American journal of physiology. Cell physiology最新文献

筛选
英文 中文
Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a posttranscriptional influence. 急性运动后骨骼肌核蛋白质组的改变揭示了转录后的影响。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-09-01 Epub Date: 2025-08-11 DOI: 10.1152/ajpcell.00575.2024
Ryan A Martin, Xiping Zhang, Mark R Viggars, James A Sanford, Zane W Taylor, Joshua R Hansen, Geremy C Clair, Collin M Douglas, Stuart J Hesketh, Joshua N Adkins, Karyn A Esser
{"title":"Alterations of the skeletal muscle nuclear proteome after acute exercise reveals a posttranscriptional influence.","authors":"Ryan A Martin, Xiping Zhang, Mark R Viggars, James A Sanford, Zane W Taylor, Joshua R Hansen, Geremy C Clair, Collin M Douglas, Stuart J Hesketh, Joshua N Adkins, Karyn A Esser","doi":"10.1152/ajpcell.00575.2024","DOIUrl":"10.1152/ajpcell.00575.2024","url":null,"abstract":"<p><p>Exercise is firmly established as a key contributor to overall well-being and is frequently employed as a therapeutic approach to mitigate various health conditions. One pivotal aspect of the impact of exercise lies in the systemic transcriptional response, which underpins its beneficial adaptations. Although extensive research has been devoted to understanding the transcriptional response to exercise, our knowledge of the protein constituents of nuclear processes accompanying gene expression in skeletal muscle remains largely elusive. We hypothesize that alterations in the nuclear proteome following exercise hold vital clues for comprehending exercise-induced transcriptional regulation and related nuclear functions. We first detail the successful isolation of skeletal muscle nuclei from C57BL/6 mice, encapsulating 2,030 proteins linked to nuclear processes such as transcription, RNA processing, chromatin modifications, and nuclear transport. We then used this approach to isolate muscle nuclei in sedentary, immediately post-, 1-h, and 4-h after a 30-min treadmill running session, to gain insight into the nuclear proteome after exercise. We found 54 proteins linked to mRNA splicing and nucleocytoplasmic transport, many of which were substantially reduced immediately postexercise followed by a rapid increase 1- and 4-h postexercise. Super-resolution microscopy experiments highlight localization changes in mRNA processing proteins postexercise, further suggesting changes in nuclear transport dynamics. Our data provide important insight into changes in the nuclear proteome following exercise. In particular, it highlights proteins contributing to mRNA processing and splicing in addition to transcriptional processes, with exercise offering broader changes in mechanisms modulating the molecular response to acute exercise.<b>NEW & NOTEWORTHY</b> Exercise plays a crucial role in promoting muscle health, but our understanding of nuclear proteins orchestrating the molecular response to exercise is limited. Isolation of skeletal muscle nuclei coupled with mass spectrometry enhanced the identification of nuclear proteins. This approach was used to investigate the temporal changes in the muscle nuclear proteome postexercise, including proteins linked to posttranscriptional processing and nuclear transport. Our findings offer new insights into potential mechanisms contributing to exercise-induced adaptations.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C953-C971"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SPP1 regulates alveolar type 2 cell-macrophage cross talk and epithelial cell fate in iron-driven lung fibrosis. 铁驱动型肺纤维化中SPP1调控肺泡2型细胞-巨噬细胞串扰和上皮细胞命运。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 10.1152/ajpcell.00140.2025
Xinqian Du, Xinyu Zhang, Zhe Wang, Dan Wang, Yunqi Li, Zengqing Liu, Qing Miao, Hanxiao Zhang, Luo Duan, Yue Hu, Muzhi Zhang, Jie Liu, Zhe Lv, Yan Chen, Wei Wang, Ying Sun, Ye Cui
{"title":"SPP1 regulates alveolar type 2 cell-macrophage cross talk and epithelial cell fate in iron-driven lung fibrosis.","authors":"Xinqian Du, Xinyu Zhang, Zhe Wang, Dan Wang, Yunqi Li, Zengqing Liu, Qing Miao, Hanxiao Zhang, Luo Duan, Yue Hu, Muzhi Zhang, Jie Liu, Zhe Lv, Yan Chen, Wei Wang, Ying Sun, Ye Cui","doi":"10.1152/ajpcell.00140.2025","DOIUrl":"10.1152/ajpcell.00140.2025","url":null,"abstract":"<p><p>Pulmonary fibrosis, a life-threatening respiratory condition affecting millions globally, is characterized by progressive lung scarring that severely compromises respiratory function. With few effective treatment options available, it carries a poor prognosis for those affected. Disrupted iron homeostasis is increasingly implicated in its pathogenesis, yet the precise mechanisms linking iron overload to fibrotic progression remain elusive. This study unveils a novel pathway by which iron accumulation orchestrates fibrotic remodeling via secreted phosphoprotein 1 (SPP1)-mediated reprogramming of alveolar type 2 (AT2) cells. Using an integrated approach combining analysis of public single-cell and single-nucleus RNA sequencing datasets with functional validation across multiple murine models of pulmonary fibrosis (iron-induced, bleomycin-induced, and silica-induced), we demonstrate that iron overload within AT2 cells triggers a coordinated transcriptional cascade affecting iron handling, immune cell recruitment, and cellular differentiation. Mechanistically, SPP1 emerges as a key mediator, functioning both externally as a paracrine signal for macrophage recruitment following iron-induced secretion from AT2 cells and internally as a driver of pathological epithelial transitions, specifically fostering the development of a <i>Krt8</i><sup>+</sup> alveolar intermediate phenotype. The clinical relevance of these findings is substantiated by analysis of human idiopathic pulmonary fibrosis specimens using publicly available single-cell and spatial transcriptomic datasets. These analyses reveal conserved pathway activation and a distinctive spatial organization of SPP1-expressing AT2 cells within remodeled tissue microenvironments, notably in close proximity to macrophages. By establishing SPP1 as a critical nexus between iron dysregulation and fibrotic progression, our work identifies the SPP1 signaling axis as a compelling therapeutic target for this devastating condition.<b>NEW & NOTEWORTHY</b> This study reveals a novel mechanism linking iron dysregulation to pulmonary fibrosis through SPP1-mediated reprogramming of alveolar type 2 cells. We demonstrate SPP1's dual role: externally coordinating macrophage recruitment and internally directing pathological epithelial transitions toward a <i>Krt8</i><sup>+</sup> intermediate state. These findings, validated across multiple mouse models and human specimens, identify the SPP1 signaling axis as a promising therapeutic target, offering new hope for treating this devastating condition where treatment options have historically been limited.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C779-C800"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Small molecule oxybutynin rescues proliferative capacity of complex III-defective muscle progenitor cells. 小分子奥昔布宁恢复复合体iii缺陷肌祖细胞的增殖能力。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-09-01 Epub Date: 2025-07-31 DOI: 10.1152/ajpcell.00141.2025
Yue Qu, Kaydine Edwards, Muying Li, Matthew Williams, Yang Liu, Pei-Yin Tsai, Chloe Cheng, Jamie Blum, Noel Acor, Tenzin Oshoe, Claire Walter, Venkatesh Thirumalaikumar, Anna Thalacker-Mercer, Aleksandra Skirycz, Joeva J Barrow
{"title":"Small molecule oxybutynin rescues proliferative capacity of complex III-defective muscle progenitor cells.","authors":"Yue Qu, Kaydine Edwards, Muying Li, Matthew Williams, Yang Liu, Pei-Yin Tsai, Chloe Cheng, Jamie Blum, Noel Acor, Tenzin Oshoe, Claire Walter, Venkatesh Thirumalaikumar, Anna Thalacker-Mercer, Aleksandra Skirycz, Joeva J Barrow","doi":"10.1152/ajpcell.00141.2025","DOIUrl":"10.1152/ajpcell.00141.2025","url":null,"abstract":"<p><p>Mitochondrial disease encompasses a group of genetically inherited disorders hallmarked by an inability of the respiratory chain to produce sufficient ATP. These disorders present with multisystemic pathologies that predominantly impact highly energetic tissues such as skeletal muscle. There is no cure or effective treatment for mitochondrial disease. We have discovered a small molecule known as oxybutynin that can bypass complex III mitochondrial dysfunction in primary murine and human skeletal muscle progenitor cells (MPCs). Oxybutynin administration improves MPC proliferative capacity, enhances cellular glycolytic function, and improves myotube formation. Mechanistically, results from our isothermal shift assay indicate that oxybutynin interacts with a suite of proteins involved in mRNA processing, which then trigger the upregulation of biological pathways to circumvent CIII mitochondrial dysfunction. Taken together, we provide evidence for the small molecule oxybutynin as a potential therapeutic candidate for the future treatment of CIII mitochondrial dysfunction.<b>NEW & NOTEWORTHY</b> Mitochondrial disease currently has no cure and affects highly energetic tissues such as skeletal muscle. Under disease conditions, the stem cell pool of the tissue is depleted and has reduced regenerative capacity, resulting in functional decline of the muscle. Here, we have identified the small molecule oxybutynin as a potential treatment option, as it improved the regenerative capacity of skeletal muscle stem cells harboring a complex III mitochondrial disease mutation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C911-C923"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ablation of UCP-1+ cells impacts FAP dynamics in muscle regeneration. 消融UCP-1+细胞影响肌肉再生中的FAP动力学。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-09-01 Epub Date: 2025-07-28 DOI: 10.1152/ajpcell.00249.2025
Jacob C Parson, Gretchen A Meyer
{"title":"Ablation of UCP-1+ cells impacts FAP dynamics in muscle regeneration.","authors":"Jacob C Parson, Gretchen A Meyer","doi":"10.1152/ajpcell.00249.2025","DOIUrl":"10.1152/ajpcell.00249.2025","url":null,"abstract":"<p><p>Uncoupling protein-1 (UCP-1+) cells found in brown adipose tissue and subtypes of white (a.k.a. beige) adipose tissue have been a focus of intensive investigation for their role in energy metabolism and are emerging as potential endocrine regulators of physiology. More recently, UCP-1+ subpopulations have also been found in skeletal muscle fibro-adipogenic progenitors (FAPs), which play an important role in regeneration. Both UCP-1+ adipocytes and FAPs secrete promyogenic cytokines further supporting their potential for proregenerative signaling. To investigate whether signaling from UCP-1+ cells does indeed promote regeneration, we examined injury-induced muscle regeneration in a mouse model with constitutive UCP-1+ cell ablation (UCP1-DTA) at three time points: early [3 and 7 days post injury (dpi)], intermediate (14 dpi), and late (21 dpi). We hypothesized that without UCP-1+ cells, muscle regeneration would be impaired at all time points. At 3 and 7 dpi, we found significantly reduced numbers of FAPs in male UCP1-DTA mice, but with no accompanying changes in muscle-derived stem (satellite) cells or immune cells. However, at 14 dpi, we observed significantly higher numbers of FAP in male UCP1-DTA mice and evidence of ongoing early-phase regeneration, including significantly increased histological and gene expression of early regenerative markers and significantly smaller regenerating fibers. However, these changes were not associated with fibrosis and fatty infiltration typical of impaired regeneration, nor were differences in contractile force recovery observed between genotypes. These findings suggest that UCP-1+ cells (adipocytes or FAPs) may regulate FAP dynamics in early regeneration, but without major effects on the recovery of structure and function.<b>NEW & NOTEWORTHY</b> Accumulating evidence suggests that UCP-1+ brown and beige adipose tissue impact muscle metabolism and that UCP-1+ FAPs impact atrophy, fibrosis, and fatty infiltration in a chronic injury model. This is the first report to examine muscle regeneration in the absence of brown fat and to explore the loss (rather than the addition) of UCP-1+ FAPs. We find that loss of both UCP-1+ adipocytes and FAPs only mildly impacts muscle regeneration, without disturbance of structural or functional recovery.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C754-C767"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The sulfation pattern of glycosaminoglycans in human brain development and neurological disorders such as Alzheimer's disease. 糖胺聚糖在人脑发育和阿尔茨海默病等神经系统疾病中的硫酸化模式。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-09-01 Epub Date: 2025-07-31 DOI: 10.1152/ajpcell.00842.2024
Kazumi Hirano, Hideo Egawa, Shoko Nishihara
{"title":"The sulfation pattern of glycosaminoglycans in human brain development and neurological disorders such as Alzheimer's disease.","authors":"Kazumi Hirano, Hideo Egawa, Shoko Nishihara","doi":"10.1152/ajpcell.00842.2024","DOIUrl":"10.1152/ajpcell.00842.2024","url":null,"abstract":"<p><p>Glycosaminoglycans (GAGs) are modified by various sulfotransferases and endosulfatases. The resulting sulfation patterns are formed, influencing numerous functions. Sulfation leads to a strong negative charge on GAGs, inducing specific interactions with proteins such as signaling ligands and pathogenicity factors, impacting cellular functions and disease onset. Although a long history of research has greatly advanced our understanding of GAGs and the sulfation patterns in model organisms, studies of human brain development and the pathogenesis of neurological diseases are in their infancy. To elucidate the role of the sulfation patterns in the human brain, it is necessary to determine the interplay of factors such as core proteins, GAG elongation enzymes, and sulfotransferases in a hierarchical manner. In recent years, technological advances in, for example, genomic mutation analysis, single-cell analysis, and in vitro brain development models, have begun to inform our understanding of the role of the sulfation patterns in human brain development and neurological disorders such as Alzheimer's disease.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C801-C811"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cholecystokinin receptor expression and signaling remain constant across time of day in rat vagal afferent neurons. 大鼠迷走神经传入神经元中胆囊收缩素受体的表达和信号传导在一天中的不同时间保持不变。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-09-01 Epub Date: 2025-07-31 DOI: 10.1152/ajpcell.00484.2025
Rachel A Arnold, BreeAnne Peterson, James Henry Peters
{"title":"Cholecystokinin receptor expression and signaling remain constant across time of day in rat vagal afferent neurons.","authors":"Rachel A Arnold, BreeAnne Peterson, James Henry Peters","doi":"10.1152/ajpcell.00484.2025","DOIUrl":"10.1152/ajpcell.00484.2025","url":null,"abstract":"<p><p>Circadian rhythms are endogenous biological clocks that regulate physiology and behaviors, such as food intake, and are synchronized by the environmental light/dark cycle. The nucleus of the solitary tract (NTS) receives excitatory glutamatergic inputs from vagal afferent neurons that innervate the gastrointestinal tract and are sensitive to the gut peptide cholecystokinin (CCK), which is released following food intake to promote satiation. Previously, we observed that NTS membrane properties, neurotransmission, and action potential firings were all under circadian control. Although it is well established that the food intake varies with the light/dark cycle, circadian variations in the cellular actions of CCK on vagal afferent neurons remain unknown. Here, we test the extent to which CCK signaling on vagal afferents and the NTS changes as a function of time of day. We used RT-qPCR and functional cellular measurements to measure gene expression and responses to CCK across the time of day in rats. Although we confirmed the presence of rhythmic clock gene expression in vagal afferent neurons, we found that CCK1 receptors did not show diurnal rhythmicity. We also observed that CCK-induced calcium responses were consistent during the day and night in dissociated vagal afferent neurons. Similarly, CCK-driven increases in spontaneous glutamate release were also constant across the light cycle at the vagal afferent-NTS synapse. We conclude that vagal afferent CCK signaling remains constant across the light cycle, and CCK1 receptors provide a consistent point of reference independent of the time of day.<b>NEW & NOTEWORTHY</b> Daily rhythms govern feeding and the processes of satiation conveyed by cholecystokinin acting on vagal afferent neurons. Yet, the putative changes in efficacy and direct cellular effects of CCK on vagal afferents across the time of day remain unknown. Here, we report constant CCK1 receptor expression and signaling in vagal afferents across the light cycle. This model indicates a fixed point of reference for CCK signaling in parallel to documented circadian changes in feeding neurocircuitry.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C812-C820"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ketone body β-hydroxybutyrate-mediated histone β-hydroxybutyrylation upregulates lipolysis and attenuates metabolic syndrome. 酮体β-羟基丁酸介导的组蛋白β-羟基丁酸基化上调脂肪分解,减轻代谢综合征。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-09-01 Epub Date: 2025-07-28 DOI: 10.1152/ajpcell.00453.2025
Sachin Aryal, Blair Mell, Ishan Manandhar, Beng San Yeoh, Xue Mei, Oluwatosin Mautin Akinola, Wisdom Ahlidja, Bina Joe
{"title":"Ketone body β-hydroxybutyrate-mediated histone β-hydroxybutyrylation upregulates lipolysis and attenuates metabolic syndrome.","authors":"Sachin Aryal, Blair Mell, Ishan Manandhar, Beng San Yeoh, Xue Mei, Oluwatosin Mautin Akinola, Wisdom Ahlidja, Bina Joe","doi":"10.1152/ajpcell.00453.2025","DOIUrl":"10.1152/ajpcell.00453.2025","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) is on the rise globally. Features of MetS include obesity, hypertension, and abnormal glucose tolerance. Exercise, keto diets, and intermittent fasting are lifestyle modifications recommended to lower MetS, all of which increase the production of the endogenous ketone body β-hydroxybutyrate. β-hydroxybutyrate has signaling and epigenetic effects, but the epigenetic mechanisms by which β-hydroxybutyrate could regulate MetS are understudied. Our previous work demonstrates that exogenous β-hydroxybutyrate supplementation lowers hypertension. The mechanism was traced to a key modification of histone-3 lysine 9 via β-hydroxybutyrylation, which remodeled the epitranscriptome to increase the accessibility of chromatin to transcriptionally upregulate key lipolytic genes, <i>Hmgcs2</i>, <i>Cyp2d4</i>, <i>Cyp2e1</i>, and <i>Acaa1b</i>. Since lipolysis is also favorable for lowering MetS, here we hypothesized that β-hydroxybutyrate lowers MetS via upregulation of these lipolytic target genes of histone β-hydroxybutyrylation. Inbred low-capacity runner (LCR/Tol) rats were used as models of MetS and treated with or without 20% (vol/vol) 1,3-butanediol, a precursor to β-hydroxybutyrate. Rats receiving 1,3-butanediol supplementation elevated circulating β-hydroxybutyrate. In addition, histones isolated from kidneys, livers, hearts, and skeletal muscle showed increased histone-3 lysine 9 β-hydroxybutyrylation and significant transcriptional upregulation of bona fide lipolytic target genes of histone-3 lysine 9 β-hydroxybutyrylation, <i>Hmgcs2</i>, <i>Cyp2d4</i>, <i>Cyp2e1</i>, and <i>Acaa1b</i> demonstrating sex-specific patterns. Furthermore, animals treated with 1,3-butanediol demonstrated significantly lower body weight, blood pressure, and blood glucose, with no adverse hepatic effects. Collectively, these data uncover the epigenetic effect of β-hydroxybutyrate via histone β-hydroxybutyrylation in multiple tissues as an underlying novel mechanism contributing to the observed beneficial effect of β-hydroxybutyrate to lower MetS.<b>NEW & NOTEWORTHY</b> This is the first study to demonstrate that exogenous β-hydroxybutyrate supplementation attenuates metabolic syndrome (MetS) and identifies histone β-hydroxybutyrylation-mediated chromatin remodeling as one of the mechanisms to upregulate the transcription of the lipid catabolic genes, <i>Hmgcs2</i>, <i>Cyp2d4, Cyp2e1</i>, and <i>Acaa1b</i>. Our work constitutes a strong foundation for the use of 1,3-butanediol as an alternative epigenetic therapeutic for individuals who are physically unable to achieve the MetS lowering benefits of lifestyle modifications such as exercise and intermittent fasting.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C726-C743"},"PeriodicalIF":4.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gut microbiome promotes succinate-induced ulcerative colitis by enhancing glycolysis through SUCNR1/NF-κB signaling pathway. 肠道微生物组通过SUCNR1/NF-κB信号通路促进糖酵解,促进琥珀酸诱导的溃疡性结肠炎。
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-08-01 Epub Date: 2025-06-23 DOI: 10.1152/ajpcell.00411.2025
Long Huo, Qian Chen, Sailei Jia, Yuli Zhang, Lihui Wang, Xian Li, Zan Li, Boyun Sun, Jingyi Shan, Jiang Lin, Lili Yang, Hua Sui
{"title":"Gut microbiome promotes succinate-induced ulcerative colitis by enhancing glycolysis through SUCNR1/NF-κB signaling pathway.","authors":"Long Huo, Qian Chen, Sailei Jia, Yuli Zhang, Lihui Wang, Xian Li, Zan Li, Boyun Sun, Jingyi Shan, Jiang Lin, Lili Yang, Hua Sui","doi":"10.1152/ajpcell.00411.2025","DOIUrl":"10.1152/ajpcell.00411.2025","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic recurrent inflammatory disease. Previous studies demonstrate that excessive accumulation of gut microbial metabolites, especially succinate, increases the risk of disease progression. However, the role of succinate and its molecular mechanism have not been explored. We investigated the effects of succinate on colonic inflammation and intestinal microbiota and their association with succinate receptor (SUCNR1) signaling in 3% dextran sodium sulfate (DSS)-induced acute UC in C57BL/6J mice. After treatment, fecal bacteria from UC mice were evaluated by 16S rRNA sequencing. Colon tissues and cell lysates were collected and prepared for histological evaluation, immunohistochemistry, Western blotting, and inflammatory activity cytokine analysis. It was found that <i>Phascolarctobacterium</i> spp. (<i>Phascolarctobacterium faecium</i>), which consumed succinate, significantly decreased SUCNR1 expression, relieved colonic damage, reduced cytokine levels, and restored the integrity of the intestinal epithelial barrier in UC mice. In addition, the results of flow cytometry, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay indicated that succinate deficiency markedly suppressed secretion of proinflammatory cytokines (e.g., interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α). Moreover, the SUCNR1 inhibitor (NF-56-EJ40) inhibited glycolysis of intestinal epithelial cells (IECs) in the coculture system with Th17 cells, including downregulation of oxygen consumption rate and increased extracellular acidification rate reflecting overall glycolytic flux, and regulated the expression of glycolysis-related proteins, such as GLUT1, HK-II, and LDHA. Collectively, our findings indicate that microbiota consumption of succinate can ameliorate DSS-induced UC through suppressing Th17, reducing IEC glycolysis, lowering the secretion of proinflammatory cytokines, maintaining epithelial barrier function, and improving dysbiosis.<b>NEW & NOTEWORTHY</b> The gut microbiota contributes to host physiology through the production of a myriad of metabolites. Owing to the high degree of cross talk both within and between biological kingdoms, metabolite-focused research has identified multiple actionable microbial targets that are relevant for host health. In this study, we demonstrated that the microbiota consumption of succinate can alleviate DSS-induced UC in mice responses by modulating glycolytic metabolism through the SUCNR1/NF-κB signaling pathway.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C440-C454"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of HIV-encoded proteins in cardiovascular disease. hiv编码蛋白在心血管疾病中的作用
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-08-01 Epub Date: 2025-07-11 DOI: 10.1152/ajpcell.00379.2025
Laszlo Kovacs, Beryl N Khakina, Eric J Belin de Chantemèle
{"title":"Role of HIV-encoded proteins in cardiovascular disease.","authors":"Laszlo Kovacs, Beryl N Khakina, Eric J Belin de Chantemèle","doi":"10.1152/ajpcell.00379.2025","DOIUrl":"10.1152/ajpcell.00379.2025","url":null,"abstract":"<p><p>Thanks to the efficacy of combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) infection, once considered a terminal diagnosis, has transformed into a chronic, manageable condition. Consequently, mortality from opportunistic infections has significantly declined, with cardiovascular disease now emerging as the leading cause of death among people living with HIV (PLWH). Along with traditional risk factors like smoking, dyslipidemia, metabolic syndrome, and combination antiretroviral therapy (cART), HIV-encoded proteins have emerged as direct etiologies of cardiovascular pathology. These viral proteins have been shown to exert pathogenic effects through mechanisms that result in endothelial activation, chronic inflammation, oxidative stress, and vascular remodeling. Although many studies have investigated the direct effects of these viral proteins on cells in culture, the pathophysiological relevance of the alterations reported often remains to be established in an in vivo setting. This mini-review provides a brief overview of the role of these proteins in HIV-related cardiovascular (CV) complications.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C592-C598"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Generation of a novel lung fibrosis model using precision-cut lung slices from transgenic TGFβ1 mice. 利用转基因tgf - β1小鼠的精确肺切片建立新型肺纤维化模型。
IF 4.7 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2025-08-01 Epub Date: 2025-07-21 DOI: 10.1152/ajpcell.00015.2025
Yanzhe Liu, Paris C Papagianis, Zifra S C de Kuijper, Julia G Chitty, Belinda Thomas, Theo Borghuis, Rianne M Jongman, Janesh Pillay, Elizabeth A Richards, Barbro N Melgert, Janette K Burgess, Jane E Bourke
{"title":"Generation of a novel lung fibrosis model using precision-cut lung slices from transgenic TGFβ1 mice.","authors":"Yanzhe Liu, Paris C Papagianis, Zifra S C de Kuijper, Julia G Chitty, Belinda Thomas, Theo Borghuis, Rianne M Jongman, Janesh Pillay, Elizabeth A Richards, Barbro N Melgert, Janette K Burgess, Jane E Bourke","doi":"10.1152/ajpcell.00015.2025","DOIUrl":"10.1152/ajpcell.00015.2025","url":null,"abstract":"<p><p>Lung fibrosis is a progressive, lethal disease with a life expectancy of 3-5 yr after diagnosis. A dysregulated repair response to injury, resulting in an accumulation of extracellular matrix (ECM) in the alveolar spaces, is suggested to be causal. Despite increased understanding of the mechanisms driving the development and progression of lung fibrosis, there is no cure. This study aimed to establish an ex vivo model of early lung fibrosis in mouse precision-cut lung slices (PCLS) derived from transgenic mice with doxycycline (DOX)-induced overexpression of active transforming growth factor β1 (TGFβ1). PCLS were untreated (control) or treated with either DOX (25 μg/mL) to induce endogenous TGFβ1 secretion ex vivo or DOX with an additional fibrotic cocktail (FC). Treatment with exogenous TGFβ1 acted as a control for the model. None of the treatments affected PCLS viability. DOX-treated PCLS secreted more TGFβ1 and pro-COL1α1 compared with control after 5 days of culture. The combination of DOX + FC induced enhanced collagen deposition with disorganized immature collagen I fibers, particularly around airways. More fibulin-1 was deposited in PCLS treated with DOX + FC compared with DOX alone, indicating that fibulin-1 may play a role in collagen deposition. In summary, ex vivo treatment with DOX induces secretion of endogenous TGFβ1 from transgenic mice PCLS, eliciting a range of profibrotic responses. The addition of FC components enhanced in situ fibrosis, especially around the airways. This novel ex vivo model may provide a platform to explore the mechanisms underlying fibrogenesis in lung fibrosis.<b>NEW & NOTEWORTHY</b> Induction of endogenous transforming growth factor β1, combined with factors increased in lungs of patients with lung fibrosis, in murine precision-cut lung slices provided an innovative ex vivo model for studying lung fibrosis. Leveraging this model revealed the involvement of extracellular matrix modulating components that may be important for orchestrating collagen fiber organization in fibrosis. This ex vivo model provides a platform to explore mechanisms underlying lung fibrosis and identify novel potential therapeutic targets.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C611-C623"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信