The FASEB Journal最新文献_第2页

Ptgs2+ CPTC Function as a “Force-Immune Axis” by Responding to Acupuncture and Mediating M2 Macrophage Activation for Anti-Inflammatory Effects Ptgs2+ CPTC作为“力-免疫轴”响应针刺和介导M2巨噬细胞活化抗炎作用

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-29 DOI: 10.1096/fj.202501175RR

Zhenwei Zhang, Haixiang Huang, Jianming Yue, Xudong Zhu, Yeping Shi, Bingbing Shen, Qianmei Zhu, Lu Mei, Qiusheng Chen

{"title":"Ptgs2+ CPTC Function as a “Force-Immune Axis” by Responding to Acupuncture and Mediating M2 Macrophage Activation for Anti-Inflammatory Effects","authors":"Zhenwei Zhang, Haixiang Huang, Jianming Yue, Xudong Zhu, Yeping Shi, Bingbing Shen, Qianmei Zhu, Lu Mei, Qiusheng Chen","doi":"10.1096/fj.202501175RR","DOIUrl":"10.1096/fj.202501175RR","url":null,"abstract":"<p>Recent advancements have highlighted the imperative for cytological exploration of fascial tissues. Telocytes, specialized interstitial cells found in connective tissues such as fascia, have garnered significant attention. Our study explored the cellular landscape of the abdominal midline fascia (AMF), revealing a primary presence of Cd34+/Pdgfra+ telocytes (CPTCs) by single-cell sequencing and cytomorphology. We identified six CPTC subpopulations with deep learning, notably Ptgs2+ CPTCs, which exhibited remarkable responsiveness to mechanical stimulus. Following the acupuncture stimulation at the special acupoints along the AMF in dysenteric rats, the proportion of Ptgs2+ CPTCs increased significantly, with these cells exhibiting strengthened cell adhesion with all CPTC subpopulations. Importantly, Ptgs2+ CPTCs activated M2 macrophages through the Il6–Il6st–Stat3 pathway, promoting anti-inflammatory responses. For the first time, our findings established Ptgs2+ CPTCs as a key “force–immune axis” that linked mechanical stimulation and immune modulation, advancing our understanding of the cellular mechanisms behind acupuncture and its potential to modulate inflammation in immune-related disorders.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187290","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

EXOSC10, an Exosome-Associated RNase, Is Essential for Mouse Spermatogonia Maintenance and Spermatogenesis EXOSC10是一种外泌体相关rna酶，对小鼠精原细胞维持和精子发生至关重要。

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-29 DOI: 10.1096/fj.202502504R

Xu Fan, Meiyang Zhou, Hong Li, Xiao Wang, Ling Yang, Jingyi Li, Nana Li, Zhengpin Wang

{"title":"EXOSC10, an Exosome-Associated RNase, Is Essential for Mouse Spermatogonia Maintenance and Spermatogenesis","authors":"Xu Fan, Meiyang Zhou, Hong Li, Xiao Wang, Ling Yang, Jingyi Li, Nana Li, Zhengpin Wang","doi":"10.1096/fj.202502504R","DOIUrl":"10.1096/fj.202502504R","url":null,"abstract":"<div>\u0000 \u0000 <p>Mammalian spermatogenesis comprises three phases: the mitotic phase of spermatogonia (involving self-renewal and proliferation), the meiotic phase of spermatocytes (producing haploid round spermatids), and the spermiogenic phase (transforming round spermatids into spermatozoa). This process depends critically on maintaining a normal transcriptome and proteome. While recent studies demonstrated that conditional knockout of <i>Exosc10</i> in male germ cells prior to meiosis disrupts meiosis, causing spermatogenic defects and male infertility, the role of EXOSC10 in spermatogonial maintenance remained unknown. This study reveals the critical role of EXOSC10 in maintaining mouse spermatogonia. Knockout of <i>Exosc10</i> in embryonic (E15.5) male germ cells using <i>Ddx4-Cre</i> mice disrupts spermatogonial maintenance. This is manifested by reduced germ cell proliferation, arrested spermatogenesis, failed sperm production, and consequent male infertility. Transcriptomic and proteomic analyses confirmed that <i>Exosc10</i> deficiency disrupts the expression of genes and proteins associated with spermatogenesis, ribosome biogenesis, germline stem cell maintenance, and regulation of reproductive processes, thereby impairing spermatogonial maintenance and blocking spermatogenesis. In summary, this study highlights that EXOSC10 safeguards normal sperm production and male fertility by maintaining the transcriptome and proteome essential for spermatogenesis, particularly at the spermatogonial stage.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187319","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

Establishment and Application of a 16-Loci STR Method for Rat Cell Line Authentication 大鼠细胞系鉴定16位点STR方法的建立与应用

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-26 DOI: 10.1096/fj.202501145R

Meimei Yang, Ting Xu, Nan Li, Yidan Sun, Wei Huang, Xuanyi Liang, Chao Shen

{"title":"Establishment and Application of a 16-Loci STR Method for Rat Cell Line Authentication","authors":"Meimei Yang, Ting Xu, Nan Li, Yidan Sun, Wei Huang, Xuanyi Liang, Chao Shen","doi":"10.1096/fj.202501145R","DOIUrl":"https://doi.org/10.1096/fj.202501145R","url":null,"abstract":"<div>\u0000 \u0000 <p>Cell line cross-contamination has been a longstanding issue in cell biology, with short tandem repeat (STR) analysis widely regarded as the gold standard for cell line authentication. However, until now, there have been few reports focused on authenticating rat cell lines. In a significant advancement, we have developed a 16-loci STR method specifically for rat cell line authentication. Using this method, we successfully distinguished 26 different rat cell lines, demonstrating the high resolution and reliability of our approach. Furthermore, we have generated and made publicly available a comprehensive rat STR database, which is unprecedented in the field. This database facilitates data comparison and validation, providing researchers with a critical resource to ensure the accuracy and integrity of their cell-based studies. Our work marks the first report on a dedicated rat STR method and the establishment of a corresponding STR database, representing a major step forward in advancing the reliability and reproducibility of rat cell line research. This development not only enhances the ability to authenticate rat cell lines but also sets a new benchmark for maintaining the purity and validity of experimental outcomes in this important model organism.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135780","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 the Chest Wall in Newborn Respiratory Function at Birth 新生儿出生时胸壁在新生儿呼吸功能中的作用

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-26 DOI: 10.1096/fj.202502372R

C. Diedericks, K. J. Crossley, I. M. Davies, D. A. Blank, S. J. E. Cramer, M. J. Wallace, A. B. te Pas, M. J. Kitchen, S. B. Hooper

{"title":"Role of the Chest Wall in Newborn Respiratory Function at Birth","authors":"C. Diedericks, K. J. Crossley, I. M. Davies, D. A. Blank, S. J. E. Cramer, M. J. Wallace, A. B. te Pas, M. J. Kitchen, S. B. Hooper","doi":"10.1096/fj.202502372R","DOIUrl":"https://doi.org/10.1096/fj.202502372R","url":null,"abstract":"<p>The chest wall significantly impacts respiratory function after birth, but its role in the newborn remains poorly understood as it is structurally and functionally different from adults. In neonates, the chest wall is highly compliant, which allows it to expand to accommodate the incoming air and the lung liquid cleared into the pulmonary interstitium during lung aeration. However, the high neonatal chest wall compliance predisposes it to distortion, which reduces breathing efficiency and necessitates respiratory muscle activation to stabilize it. This increases the work of breathing and, when combined with fewer fatigue-resistant Type I muscle fibers (slow twitch, high oxidative capacity) in the diaphragm muscle, the risk of respiratory fatigue is increased. Nevertheless, as the chest wall is highly compliant in the newborn, recent studies have demonstrated that extra-thoracic pressures can influence chest wall mechanics. Positive extra-thoracic pressures (such as those applied with tight swaddling) limit chest wall expansion, whereas a small constant negative extra-thoracic pressure stabilizes the chest wall and improves oxygenation in neonates. In this review, we aim to summarize the current evidence on chest wall function in fetuses and neonates, particularly during lung liquid clearance, lung aeration, and breathing after birth. Furthermore, we will explore how knowledge from newborn respiratory physiology may inform our understanding of the respiratory consequences of pulmonary oedema in adults, such as occurred during the initial stages of the COVID-19 pandemic.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202502372R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135753","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

Age-Specific Biomarkers TREM1 and KLF4 in Ischemic Stroke: From Transcriptomic Discovery to Therapeutic Drug Screening 缺血性卒中的年龄特异性生物标志物TREM1和KLF4：从转录组学发现到治疗药物筛选

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-26 DOI: 10.1096/fj.202501934RR

Xin Zhou, Junlin Bi, Huayan Chen, Yan Wang, Yuxin Li, Dong Huang, Xiaoli Ma, Weiming Cai, Dongbo Jiang, Tangming Guan

{"title":"Age-Specific Biomarkers TREM1 and KLF4 in Ischemic Stroke: From Transcriptomic Discovery to Therapeutic Drug Screening","authors":"Xin Zhou, Junlin Bi, Huayan Chen, Yan Wang, Yuxin Li, Dong Huang, Xiaoli Ma, Weiming Cai, Dongbo Jiang, Tangming Guan","doi":"10.1096/fj.202501934RR","DOIUrl":"https://doi.org/10.1096/fj.202501934RR","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemic stroke (IS) is increasingly common among younger and middle-aged individuals aged 18–60 years, who exhibit different clinical profiles from older patients. This study aimed to identify key candidate genes associated with the risk of IS in younger individuals. In this study, we sourced IS datasets from GEO, conducted functional enrichment analysis, and used WGCNA to identify core gene modules, intersecting them with differentially expressed genes (DEGs) for candidate biomarkers. A logistic regression model evaluated these genes' diagnostic performance, validated through transient middle cerebral artery occlusion (tMCAO) murine models. Immune infiltration analyses characterized the immune profile of IS, while molecular docking assessed drug–target interactions with ΔG ≤ −7 kcal/mol. TREM1 and KLF4 are identified as key biomarkers for IS in younger and middle-aged individuals, confirmed by a tMCAO mouse model showing elevated expression linked to neurobehavioral outcomes. Molecular docking revealed curcumin's Vina score of −7.0 kcal/mol with TREM1, while calcitriol, nimesulide, and triptonide showed strong interactions with KLF4, scoring −8.2, −7.0, and −7.2 kcal/mol, respectively. This study highlights the importance of age-specific strategies for IS and identifies TREM1 and KLF4 as promising dual-purpose biomarkers for diagnosis and therapy, enhancing prognostic assessments and outcomes for younger patients.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135779","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

Colchicine Modulates the Actin Cytoskeleton by Direct Binding to the Monomer and Facilitating Polymerization 秋水仙碱通过直接结合单体和促进聚合调节肌动蛋白细胞骨架

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-26 DOI: 10.1096/fj.202501907R

Ebru Haciosmanoglu Aldogan, Başak Günçer, Sefer Baday, Bilge Özerman Edis, Zsolt Mártonfalvi, Gergely Agócs, Anna Hollósi, Andrea Varga, Hedvig Tordai, Miklós S. Z. Kellermayer, Ahmet Gül, Muhammet Bektaş

{"title":"Colchicine Modulates the Actin Cytoskeleton by Direct Binding to the Monomer and Facilitating Polymerization","authors":"Ebru Haciosmanoglu Aldogan, Başak Günçer, Sefer Baday, Bilge Özerman Edis, Zsolt Mártonfalvi, Gergely Agócs, Anna Hollósi, Andrea Varga, Hedvig Tordai, Miklós S. Z. Kellermayer, Ahmet Gül, Muhammet Bektaş","doi":"10.1096/fj.202501907R","DOIUrl":"https://doi.org/10.1096/fj.202501907R","url":null,"abstract":"<div>\u0000 \u0000 <p>Actin, the most abundant intracellular protein, exists in a monomeric globular form (G-actin) or as polymerized filamentous actin (F-actin), and is essential for cell morphology, motility, and intracellular transport. Colchicine is a well-established anti-inflammatory drug primarily known for binding tubulin and inhibiting microtubule polymerization, yet its full mechanism of action remains unclear. Here, we investigated whether colchicine directly modulates actin cytoskeleton dynamics. Using human monocytic and murine B-lymphoma cell lines, combined with in vitro biochemical and biophysical assays, we found that colchicine binds directly to G-actin with submicromolar affinity, enhances actin polymerization, and stabilizes F-actin. Colchicine treatment in cells shifted the F−/G-actin ratio toward the filamentous form, increased cortical actin organization, and altered cell mechanical properties. Thermal shift assays confirmed increased actin stability, while molecular docking identified two potential colchicine-binding sites—one at the ATP-binding cleft in G-actin and another at the intermonomeric interface in F-actin. These findings reveal a previously unrecognized actin-modulatory role of colchicine, providing mechanistic insight into its anti-inflammatory effects and suggesting potential applications in diseases involving actin cytoskeletal dysregulation.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135778","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

Hesperetin Alleviates Bleomycin-Induced Pulmonary Fibrosis by Modulating Cellular Senescence and Promoting Impaired Autophagy in a CISD2-Dependent Manner 橙皮素通过调节细胞衰老和促进受损自噬以cisd2依赖的方式减轻博来霉素诱导的肺纤维化

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-26 DOI: 10.1096/fj.202502311R

Qi Lin, Wenjie Fan, Ziyi Chen, Bin Chen, Chaofeng Zhang

{"title":"Hesperetin Alleviates Bleomycin-Induced Pulmonary Fibrosis by Modulating Cellular Senescence and Promoting Impaired Autophagy in a CISD2-Dependent Manner","authors":"Qi Lin, Wenjie Fan, Ziyi Chen, Bin Chen, Chaofeng Zhang","doi":"10.1096/fj.202502311R","DOIUrl":"https://doi.org/10.1096/fj.202502311R","url":null,"abstract":"<p>Pulmonary fibrosis is an age-related disease marked by progressive lung function decline and high mortality, with limited treatment options. Hesperetin, a citrus-derived flavonoid with antioxidant and anti-aging properties, has not been thoroughly investigated for its potential in pulmonary fibrosis. This study evaluated the prophylactic potential of hesperetin in pulmonary fibrosis <i>in vivo</i> and <i>in vitro</i>. <i>In vivo</i> experiments demonstrated that hesperetin can significantly reduce cellular senescence in bleomycin-induced pulmonary fibrosis. Activation of Nrf2 signaling was involved in inhibiting cellular senescence and oxidative stress in A549 cells treated with hesperetin. We found that the deficiency of CISD2 contributed to bleomycin-induced pulmonary fibrosis and was associated with the protective effects of hesperetin, which bound with high affinity to CISD2. Meanwhile, overexpression of CISD2 improved cellular senescence induced by bleomycin in vitro. This study further highlighted that the cellular senescence induced by bleomycin was associated with impaired autophagy, which might be related to the inhibition of the CISD2/BECN1 pathway through bioinformatics analysis. Additionally, hesperetin was found to restore bleomycin-induced impaired autophagy by modulating the CISD2/BECN1 pathway. Notably, the protective effects of hesperetin against pulmonary fibrosis were diminished following CISD2 knockdown. Collectively, these findings suggest that hesperetin ameliorates bleomycin-induced pulmonary fibrosis through inhibiting cellular senescence and attenuating impaired autophagy in a CISD2-dependent manner.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202502311R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135752","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

MIF Promotes Phenotypic Switching of VSMCs via AKT/mTOR-Mediated Autophagy Regulation in Aortic Dissection 在主动脉夹层中，MIF通过AKT/ mtor介导的自噬调节促进VSMCs表型转换

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-26 DOI: 10.1096/fj.202501761R

Yuting Pu, Yang Zhou, Tuo Guo, Xiaogao Pan, Xin Sun, Guifang Yang, Xiangping Chai

{"title":"MIF Promotes Phenotypic Switching of VSMCs via AKT/mTOR-Mediated Autophagy Regulation in Aortic Dissection","authors":"Yuting Pu, Yang Zhou, Tuo Guo, Xiaogao Pan, Xin Sun, Guifang Yang, Xiangping Chai","doi":"10.1096/fj.202501761R","DOIUrl":"https://doi.org/10.1096/fj.202501761R","url":null,"abstract":"<div>\u0000 \u0000 <p>Aortic dissection (AD) is a life-threatening vascular emergency characterized by vascular smooth muscle cell (VSMC) dysfunction and extracellular matrix degradation. Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine implicated in vascular remodeling, has been suggested to play a role in AD, yet its mechanistic contribution remains unclear. We integrated bulk and single-cell transcriptomic analyses with validation in human and murine AD tissues. Functional roles of MIF were explored using MIF knockout mice, pharmacological inhibition (ISO-1), and adeno-associated virus–mediated overexpression. Mechanistic studies in primary VSMCs examined autophagy flux, AKT/mTOR signaling, and phenotypic switching. Pharmacological modulation with rapamycin and chloroquine was performed to assess autophagy's role. MIF was markedly upregulated in AD tissues, especially in VSMCs. MIF deficiency or ISO-1 treatment significantly reduced AD incidence, rupture, and aortic dilation, while overexpression aggravated disease progression. Mechanistically, MIF suppressed autophagy by activating AKT/mTOR signaling, promoting the synthetic VSMC phenotype. Restoration of autophagy with rapamycin reversed MIF-induced phenotypic switching, whereas chloroquine exacerbated AD. Furthermore, AKT silencing abolished the pathological effects of MIF, and receptor-blocking experiments indicated that CD74 and CXCR2 mediate MIF-driven signaling. MIF is a critical regulator of VSMC phenotypic switching in AD through AKT/mTOR-mediated autophagy suppression. Targeting MIF or enhancing autophagy represents a potential therapeutic strategy for preventing AD progression.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135750","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

MuRF1 Partners With TRIM72 to Impair Insulin Signaling in Skeletal Muscle Cells MuRF1与TRIM72合作损害骨骼肌细胞中的胰岛素信号

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-26 DOI: 10.1096/fj.202502066RR

Ibrahim Musa, Alex Peter Seabright, Jonathan Barlow, Yusuke Nishimura

{"title":"MuRF1 Partners With TRIM72 to Impair Insulin Signaling in Skeletal Muscle Cells","authors":"Ibrahim Musa, Alex Peter Seabright, Jonathan Barlow, Yusuke Nishimura","doi":"10.1096/fj.202502066RR","DOIUrl":"https://doi.org/10.1096/fj.202502066RR","url":null,"abstract":"<p>Muscle RING-finger protein 1 (MuRF1, gene name: <i>TRIM63</i>) is well known as a critical molecular regulator in skeletal muscle atrophy. Despite the identification of several substrates and interaction partners for MuRF1, the precise molecular mechanisms by which MuRF1 causes skeletal muscle atrophy remain unclear. To gain further insight into the underlying mechanism of skeletal muscle atrophy, we applied targeted biochemical approaches and identified tripartite motif-containing protein 72 (TRIM72) as a novel MuRF1-interacting protein. Subsequent analysis using MuRF1 knockout and rescue experiments showed that TRIM72 protein abundance is dependent on the presence of MuRF1 protein. Furthermore, TRIM72 protein level was increased by dexamethasone treatment in C2C12 myotubes, alongside increased MuRF1 protein level. Dexamethasone decreases IRS1/Akt signaling and glucose uptake specifically in wild type myotubes, but not in MuRF1 KO myotubes. Further analysis showed that overexpression of TRIM72 impairs IRS1/Akt signaling without the presence of MuRF1, indicating that MuRF1 induces a negative impact on insulin signaling through a plausible cooperation with TRIM72. Our findings provide novel non-degradative molecular roles of MuRF1 that link together skeletal muscle atrophy and impaired insulin sensitivity.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 19","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202502066RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135781","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

Aerobic Exercise Regulating Arterial Function by Lactate/GPR81 Signaling Pathway 有氧运动通过乳酸/GPR81信号通路调节动脉功能。

IF 4.2 2区生物学

The FASEB Journal Pub Date : 2025-09-24 DOI: 10.1096/fj.202501374RR

Fengzhi Yu, Yilan Guo, Liang He, Manyi Zhang, Aochuan Xue, Yao Zou, Dandan Jia, Ru Wang, Peng Sun

{"title":"Aerobic Exercise Regulating Arterial Function by Lactate/GPR81 Signaling Pathway","authors":"Fengzhi Yu, Yilan Guo, Liang He, Manyi Zhang, Aochuan Xue, Yao Zou, Dandan Jia, Ru Wang, Peng Sun","doi":"10.1096/fj.202501374RR","DOIUrl":"10.1096/fj.202501374RR","url":null,"abstract":"<div>\u0000 \u0000 <p>G protein-coupled receptor 81 (GPR81) is a hydroxycarboxylic acid receptor that has been identified in recent years to be widely expressed in cells of a variety of tissues. It has been demonstrated that lactate (LA) is the sole endogenous, natural ligand for GPR81 under physiological conditions. However, the precise function of GPR81 in the regulation of arterial function remains to be elucidated. The present study constructed a mouse model of impaired arterial function by subjecting C57/BL6J female mice to a high-fat diet (HFD) and ovariectomy (OVX). The results demonstrated that mice with OVX and obesity exhibited increased arterial stiffness, accompanied by lipid metabolism disorder. Furthermore, a substantial quantity of oxidized low-density lipoprotein (ox-LDL) was observed in the aortic sinus region, which is a critical factor in the development of atherosclerosis. However, the 8-week aerobic exercise intervention was found to be capable of effectively reversing these adverse effects. Concurrently, in ovariectomized obese mice, serum LA levels exhibited a significant increase following exercise, as did the expression levels of aortic GPR81. Furthermore, an increase in cAMP-response element-binding protein 1 (CREB) phosphorylation was observed, which resulted in an enhancement of endothelial nitric oxide synthase (eNOS) expression. Finally, the study confirmed that exercise did not restore arterial function-related indices in ovariectomized obese <i>Gpr81</i> knockout mice. Thus, it was determined that exercise may enhance arterial function through the LA/GPR81/p-CREB/CREB/eNOS signaling pathway.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 18","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132332","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