American journal of physiology. Cell physiology最新文献

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Transcriptional analysis of cancer cachexia: conserved and unique features across preclinical models and biological sex. 癌症痛症的转录分析:跨临床前模型和生物性别的保守和独特特征
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1152/ajpcell.00647.2024
Francielly Morena, Ana Regina Cabrera, Ronald G Jones, Eleanor R Schrems, Ruqaiza Muhyudin, Tyrone A Washington, Kevin A Murach, Nicholas P Greene
{"title":"Transcriptional analysis of cancer cachexia: conserved and unique features across preclinical models and biological sex.","authors":"Francielly Morena, Ana Regina Cabrera, Ronald G Jones, Eleanor R Schrems, Ruqaiza Muhyudin, Tyrone A Washington, Kevin A Murach, Nicholas P Greene","doi":"10.1152/ajpcell.00647.2024","DOIUrl":"10.1152/ajpcell.00647.2024","url":null,"abstract":"<p><p>Studies suggest heterogeneity in cancer cachexia (CC) among models and biological sexes, yet examinations comparing models and sexes are scarce. We compared the transcriptional landscape of skeletal muscle across murine CC models and biological sexes during early and late CC. Global gene expression analyses were performed on gastrocnemius [Lewis lung carcinoma (LLC)], quadriceps (KPC-pancreatic), and tibialis anterior [Colon-26 (C26)-colorectal and <i>Apc<sup>Min/</sup></i><sup>+</sup>] muscles across biological sexes. Differentially expressed genes (DEGs) were identified using an adj-<i>P</i> value of <0.05, followed by pathway and computational cistrome analyses. Integrating all controls, early and late stages of all models and sexes revealed up to 68% of DEGs and pathways were enriched at early and late CC, indicating a conserved transcriptional profile during CC development. Comparing DEGs and pathways within sexes and across models, in early CC, the transcriptional response was highly heterogeneous. At late stage, 11.5% of upregulated and 10% of downregulated genes were shared between models in males, whereas 18.9% of upregulated and 7% of downregulated DEGs were shared in females. Shared DEGs were enriched in proteasome and mitophagy/autophagy pathways (upregulated), and downregulation of energy metabolism pathways in males only. Between sexes, though the proportion of shared DEGs was low (<16%), similar pathway enrichment was observed, including proteasome and mitophagy at late-stage CC. In early CC, oncostatin M receptor (<i>Osmr</i>) upregulation was the only commonality across all models and sexes, whereas CLOCK and ARNTL/BMAL1 were predicted transcriptional factors associated with dysregulations in all three male models. This study highlights sex and model differences in CC progression and suggests conserved transcriptional changes as potential therapeutic targets.<b>NEW & NOTEWORTHY</b> This study is among the first to integrate and compare the skeletal muscle transcriptional landscape across multiple preclinical models and biological sexes. We highlight that <i>1</i>) early CC transcriptional changes are two-thirds conserved at late stages, <i>2</i>) DEGs are largely model and sex specific, and <i>3</i>) transcriptional factors including CLOCK and ARNTL/BMAL1, which influence early CC gene expression, might represent a global therapeutic target with a chance of efficacy across various cancer types.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1514-C1531"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492914","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
Transcriptional regulation of olfactory receptor OR51B5 by the TBX6. TBX6 对嗅觉受体 OR51B5 的转录调控。
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1152/ajpcell.00464.2024
Jiyun Roh, Wesuk Kang, Suhjin Yang, Dabin Choi, Taesun Park
{"title":"Transcriptional regulation of olfactory receptor OR51B5 by the TBX6.","authors":"Jiyun Roh, Wesuk Kang, Suhjin Yang, Dabin Choi, Taesun Park","doi":"10.1152/ajpcell.00464.2024","DOIUrl":"10.1152/ajpcell.00464.2024","url":null,"abstract":"<p><p>Olfactory receptors (ORs) are G protein-coupled receptors primarily expressed in olfactory tissue, facilitating the perception of odors. Interestingly, they have also been detected in nonolfactory tissues such as the skin, where they regulate processes like collagen synthesis. This study aimed to analyze the promoter of the OR family 51 subfamily B member 5 (OR51B5) and identify the transcription factors that bind to it to understand the potential regulatory mechanisms for OR51B5 expression. We examined the promoter region spanning 2,000 base pairs upstream of the transcription start site and conducted a deletion analysis, revealing that the core promoter encompasses the region from -153 to -111 base pairs. A luciferase assay using various candidate transcription factors showed that the overexpression or knockdown of T-Box Transcription Factor 6 (TBX6) significantly regulated OR51B5 promoter activity, whereas other candidate transcription factors had no significant effect. In addition, we validated TBX6 binding to the OR51B5 promoter using site-directed mutation and electrophoretic mobility shift assays, and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR). This study is the first to uncover the role of TBX transcription factors in regulating OR gene expression in mammals, which may have implications for treating related disorders.<b>NEW & NOTEWORTHY</b> This study reveals that olfactory receptor OR51B5, primarily known for its role in olfaction, is significantly regulated by the transcription factor TBX6 in nonolfactory tissues. We demonstrate that TBX6 binding to the OR51B5 promoter modulates its activity, highlighting a novel regulatory mechanism for olfactory receptor expression, which could impact collagen synthesis and cell survival in human dermal fibroblasts.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1564-C1576"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492915","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
Ciliopathy organoid models: a comprehensive review. 纤毛虫病类器官模型--全面回顾。
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1152/ajpcell.00343.2024
Matylda Zofia Kuzinska, Sally Yuan-Yin Lin, Verena Klämbt, Philip Bufler, Milad Rezvani
{"title":"Ciliopathy organoid models: a comprehensive review.","authors":"Matylda Zofia Kuzinska, Sally Yuan-Yin Lin, Verena Klämbt, Philip Bufler, Milad Rezvani","doi":"10.1152/ajpcell.00343.2024","DOIUrl":"10.1152/ajpcell.00343.2024","url":null,"abstract":"<p><p>Cilia are membrane-bound organelles found on the surface of most mammalian cell types and play numerous roles in human physiology and development, including osmo- and mechanosensation, as well as signal transduction. Ciliopathies are a large group of, usually rare, genetic disorders resulting from abnormal ciliary structure or ciliary dysfunction that have a high collective prevalence. Autosomal dominant or recessive polycystic kidney disease (ADPKD/ARPKD), Bardet-Biedl-Syndrome, and primary ciliary dyskinesia (PCD) are the most frequent etiologies. Rodent and zebrafish models have improved the understanding of ciliopathy pathophysiology. Yet, the limitations of these genetically modified animal strains include the inability to fully replicate the phenotypic heterogeneity found in humans, including variable multiorgan involvement. Organoids, self-assembled three-dimensional cell-based models derived from human induced pluripotent stem cells (iPSCs) or primary tissues, can recapitulate certain aspects of the development, architecture, and function of the target organ \"in the dish.\" The potential of organoids to model patient-specific genotype-phenotype correlations has increased their popularity in ciliopathy research and led to the first preclinical organoid-based ciliopathy drug screens. This review comprehensively summarizes and evaluates current ciliopathy organoid models, focusing on kidney, airway, liver, and retinal organoids, as well as the specific methodologies used for their cultivation and for interrogating ciliary dysfunction.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1604-C1625"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567361","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
Unlocking the mechanisms of muscle fatigue: insights from the Marion J. Siegman Award Lectures. 解开肌肉疲劳的机理:马里恩-J-西格曼奖演讲的启示》:社论。
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-10-14 DOI: 10.1152/ajpcell.00620.2024
Arthur J Cheng, Nathaniel J Andrews, Thomas J Hawke
{"title":"Unlocking the mechanisms of muscle fatigue: insights from the Marion J. Siegman Award Lectures.","authors":"Arthur J Cheng, Nathaniel J Andrews, Thomas J Hawke","doi":"10.1152/ajpcell.00620.2024","DOIUrl":"10.1152/ajpcell.00620.2024","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1347-C1348"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455989","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
Advancements and future directions in American Journal of Physiology-Cell Physiology: a 2024 editorial update.
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 DOI: 10.1152/ajpcell.00862.2024
Liliana Schaefer
{"title":"Advancements and future directions in <i>American Journal of Physiology-Cell Physiology</i>: a 2024 editorial update.","authors":"Liliana Schaefer","doi":"10.1152/ajpcell.00862.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00862.2024","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":"327 6","pages":"C1681-C1685"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798697","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
Extracellular vesicle miR-206 improves chronic binge alcohol-mediated decreased myoblast differentiation in SIV-infected female macaques. 细胞外囊泡 miR-206 可改善 SIV 感染的雌性猕猴因长期酗酒而导致的成肌细胞分化下降。
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-08-05 DOI: 10.1152/ajpcell.00290.2024
Brianna L Bourgeois, Eden M Gallegos, Danielle E Levitt, Peter J Bergeaux, Patricia E Molina, Liz Simon
{"title":"Extracellular vesicle miR-206 improves chronic binge alcohol-mediated decreased myoblast differentiation in SIV-infected female macaques.","authors":"Brianna L Bourgeois, Eden M Gallegos, Danielle E Levitt, Peter J Bergeaux, Patricia E Molina, Liz Simon","doi":"10.1152/ajpcell.00290.2024","DOIUrl":"10.1152/ajpcell.00290.2024","url":null,"abstract":"<p><p>Alcohol misuse in people with human immunodeficiency virus (HIV) (PWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with increased physical frailty and impaired functional skeletal muscle mass, respectively. Previous studies by our group demonstrate that muscle-enriched microRNAs (myomiRs) are differentially expressed in skeletal muscle (SKM) from CBA-administered SIV-infected male macaques and their altered expression contributes to impaired differentiation of SKM stem cells or myoblasts. MicroRNAs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular communication. The present study tested the hypothesis that EV-mediated delivery of miR-206 can ameliorate CBA-mediated decreases in myoblast differentiation. Myoblasts were isolated from SKM of female SIV-infected, antiretroviral therapy-treated macaques that received either CBA (2.5 g/kg/day, CBA/SIV) or water (VEH/SIV) for 14.5 mo. Myotube and myotube-derived EV myomiR expression, including miR-206, was lower in the CBA/SIV group. Overexpression of miR-206 decreased histone deacetylase 4 (<i>HDAC4</i>) and paired box 7 (<i>PAX7</i>) expression in myotubes and increased fusion index, a differentiation index, in CBA/SIV-derived myotubes. Similarly, EV-mediated delivery of miR-206 increased both fusion index and myotube density of CBA/SIV-derived myoblasts. These results support the potential therapeutic utility of EVs in delivering myomiRs to improve SKM stem cell differentiation.<b>NEW & NOTEWORTHY</b> Alcohol decreases skeletal muscle myoblast differentiation into myotubes, which is associated with decreased expression of microRNA-206. We show that delivering exogenous miR-206 in plasma-derived extracellular vesicles (EVs) to myoblasts derived from alcohol-administered animals increases myotube differentiation. These results support the potential therapeutic utility of EVs in delivering muscle-enriched microRNAs to improve skeletal muscle stem cell differentiation.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1626-C1637"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888254","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
ZNF197-AS1/miR-425/GABARAPL1 axis: a novel regulatory mechanism in uveal melanoma. ZNF197-AS1/miR-425/GABARAPL1轴:葡萄膜黑色素瘤的新型调控机制
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-09-23 DOI: 10.1152/ajpcell.00457.2024
Chao Zhang, Shuai Wu
{"title":"ZNF197-AS1/miR-425/GABARAPL1 axis: a novel regulatory mechanism in uveal melanoma.","authors":"Chao Zhang, Shuai Wu","doi":"10.1152/ajpcell.00457.2024","DOIUrl":"10.1152/ajpcell.00457.2024","url":null,"abstract":"<p><p>This study investigates the role of the long noncoding RNA (lncRNA) <i>ZNF197-AS1</i> in uveal melanoma (UM), focusing on its function within a competing endogenous RNA (ceRNA) network. Using the UM-related TCGA (The Cancer Genome Atlas) dataset, we analyzed the expression levels of <i>ZNF197-AS1</i> and its correlation with <i>miR-425</i> and <i>GABARAPL1</i>, an essential autophagy-related gene. Our analysis revealed that <i>ZNF197-AS1</i> acts as a ceRNA by competitively binding to <i>miR-425</i>, resulting in the upregulation of <i>GABARAPL1</i>. This interaction plays a crucial role in the growth and metastasis of UM. The expression of <i>GABARAPL1</i> showed a strong correlation with the clinical outcomes of patients with UM. Furthermore, in vitro assays confirmed that <i>ZNF197-AS1</i> impedes UM cell proliferation, migration, and invasion by modulating the <i>miR-425/GABARAPL1</i> axis. These findings suggest that ZNF197-AS1 can effectively inhibit UM progression through this ceRNA regulatory network. This study provides valuable insights into the molecular mechanisms underlying UM and highlights the potential of targeting the <i>ZNF197-AS1/miR-425/GABARAPL1</i> axis as a therapeutic strategy for UM.<b>NEW & NOTEWORTHY</b> This study identifies the ZNF197-AS1/miR-425/GABARAPL1 axis as a novel regulatory mechanism in uveal melanoma. ZNF197-AS1 upregulates GABARAPL1 by sponging miR-425, inhibiting UM cell proliferation, migration, and invasion. This discovery highlights a potential therapeutic target, providing new insights into UM progression and patient outcomes.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1638-C1650"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279083","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
Effects of age on human skeletal muscle: a systematic review and meta-analysis of myosin heavy chain isoform protein expression, fiber size, and distribution. 年龄对人体骨骼肌的影响:肌球蛋白重链同工酶蛋白表达、纤维大小和分布的系统回顾和荟萃分析。
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-10-07 DOI: 10.1152/ajpcell.00347.2024
Christopher Lee, Philip C Woods, Amanda E Paluch, Mark S Miller
{"title":"Effects of age on human skeletal muscle: a systematic review and meta-analysis of myosin heavy chain isoform protein expression, fiber size, and distribution.","authors":"Christopher Lee, Philip C Woods, Amanda E Paluch, Mark S Miller","doi":"10.1152/ajpcell.00347.2024","DOIUrl":"10.1152/ajpcell.00347.2024","url":null,"abstract":"<p><p>Human studies examining the cellular mechanisms behind sarcopenia, or age-related loss of skeletal muscle mass and function, have produced inconsistent results. A systematic review and meta-analysis were performed to determine the aging effects on protein expression, size, and distribution of fibers with various myosin heavy chain (MyHC) isoforms. Study eligibility included MyHC comparisons between young (18-49 yr) and older (≥60 yr) adults, with 27 studies identified. Relative protein expression was higher with age for the slow-contracting MyHC I fibers, with correspondingly lower fast-contracting MyHC II and IIA values. Fiber sizes were similar with age for MyHC I, but smaller for MyHC II and IIA. Fiber distributions were similar with age. When separated by sex, the few studies that examined females showed atrophy of MyHC II and IIA fibers with age, but no change in MyHC protein expression. Additional analyses by measurement technique, physical activity, and muscle biopsies provided important insights. In summary, age-related atrophy in fast-contracting fibers lead to more of the slow-contracting, lower force-producing isoform in older male muscles, which helps explain their age-related loss in whole muscle force, velocity, and power. Exercise or pharmacological interventions that shift MyHC expression toward faster isoforms and/or increase fast-contracting fiber size should decrease the prevalence of sarcopenia. Our findings also indicate that future studies need to include or focus solely on females, measure MyHC IIA and IIX isoforms separately, examine fiber type distribution, sample additional muscles to the vastus lateralis (VL), and incorporate an objective measurement of physical activity.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1400-C1415"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387260","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
Ion channel Piezo1 induces ferroptosis of trabecular meshwork cells: a novel observation in the pathogenesis in primary open angle glaucoma. 离子通道 Piezo1 可诱导小梁网状结构细胞铁突变:原发性开角型青光眼发病机制的新发现
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1152/ajpcell.00173.2024
Kexin Liu, Jing Xu, Rufei Yang, Feng Wang, Ying Su
{"title":"Ion channel Piezo1 induces ferroptosis of trabecular meshwork cells: a novel observation in the pathogenesis in primary open angle glaucoma.","authors":"Kexin Liu, Jing Xu, Rufei Yang, Feng Wang, Ying Su","doi":"10.1152/ajpcell.00173.2024","DOIUrl":"10.1152/ajpcell.00173.2024","url":null,"abstract":"<p><p>This study aims to elucidate the role of Piezo1, a mechanosensitive molecule, in trabecular meshwork cells (TMCs) in the context of primary open angle glaucoma (POAG), a leading cause of irreversible visual impairment. Dysfunction of the trabecular meshwork (TM) is a key factor in the elevated intraocular pressure (IOP) observed in POAG, yet the specific mechanisms leading to TM dysfunction are not fully understood. We performed cell stretching on human trabecular meshwork cells (HTMCs) and pharmacologically activated HTMCs with Yoda1 to study the role of Piezo1 in HTMCs. We focused on assessing cell viability, mitochondrial changes, lipid peroxidation, and the expression of ferroptosis-related targets such as acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4). Cell stretching induces ferroptosis in HTMCs, and this phenomenon is reversed by Piezo1 knockdown. In addition, pharmacological activation of Piezo1 also leads to ferroptosis in HTMCs. Furthermore, inhibiting the JNK/p38 signaling pathway was found to mitigate the ferroptotic response induced by Yoda1, thereby confirming that Piezo1 induces ferroptosis in TMCs through this pathway. Notably, our experiments suggest that Yoda1 may trigger ferroptosis in the TM of mouse eyes. Our findings demonstrate that the Piezo1 pathway is a crucial mediator of ferroptosis in TMCs, providing new insights into the pathogenic mechanisms of glaucoma, particularly POAG. This study highlights the potential of targeting the Piezo1 pathway as a therapeutic approach for mitigating TM dysfunction and managing POAG.<b>NEW & NOTEWORTHY</b> This study is the first to show that cell stretching induces ferroptosis in trabecular meshwork cells (TMCs), dependent on Piezo1 activation. Targeting the Piezo1 pathway offers new therapeutic potential for mitigating trabecular meshwork dysfunction and managing primary open angle glaucoma (POAG). The study also reveals Piezo1 induces ferroptosis via the JNK/p38 signaling pathway.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1591-C1603"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492907","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
Targeting the gut and tumor microbiome in cancer treatment resistance. 在抗癌过程中瞄准肠道和肿瘤微生物组。
IF 5 2区 生物学
American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-10-22 DOI: 10.1152/ajpcell.00201.2024
Sona Ciernikova, Aneta Sevcikova, Michal Mego
{"title":"Targeting the gut and tumor microbiome in cancer treatment resistance.","authors":"Sona Ciernikova, Aneta Sevcikova, Michal Mego","doi":"10.1152/ajpcell.00201.2024","DOIUrl":"10.1152/ajpcell.00201.2024","url":null,"abstract":"<p><p>Therapy resistance represents a significant challenge in oncology, occurring in various therapeutic approaches. Recently, animal models and an increasing set of clinical trials highlight the crucial impact of the gut and tumor microbiome on treatment response. The intestinal microbiome contributes to cancer initiation, progression, and formation of distant metastasis. In addition, tumor-associated microbiota is considered a critical player in influencing tumor microenvironments and regulating local immune processes. Intriguingly, numerous studies have successfully identified pathogens within the gut and tumor microbiome that might be linked to a poor response to different therapeutic modalities. The unfavorable microbial composition with the presence of specific microbes participates in cancer resistance and progression via several mechanisms, including upregulation of oncogenic pathways, macrophage polarization reprogramming, metabolism of chemotherapeutic compounds, autophagy pathway modulation, enhanced DNA damage repair, inactivation of a proapoptotic cascade, and bacterial secretion of extracellular vesicles, promoting the processes in the metastatic cascade. Targeted elimination of specific intratumoral bacteria appears to enhance treatment response. However, broad-spectrum antibiotic pretreatment is mostly connected to reduced efficacy due to gut dysbiosis and lower diversity. Mounting evidence supports the potential of microbiota modulation by probiotics and fecal microbiota transplantation to improve intestinal dysbiosis and increase microbial diversity, leading to enhanced treatment efficacy while mitigating adverse effects. In this context, further research concerning the identification of clinically relevant microbiome signatures followed by microbiota-targeted strategies presents a promising approach to overcoming immunotherapy and chemotherapy resistance in refractory patients, improving their outcomes.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1433-C1450"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492910","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
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