American journal of physiology. Cell physiology最新文献

{"title":"TRIB1: A Multifaceted Regulator of Cardiometabolic Health.","authors":"Valeria Prete, Paola Di Pietro, Angela Carmelita Abate, Eleonora Venturini, Concetta Iside, Carmine Vecchione, Albino Carrizzo","doi":"10.1152/ajpcell.00231.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00231.2025","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. The rising prevalence of CVD is primarily driven by several risk factors, including dyslipidemia, atherosclerosis, diabetes and obesity. Many current studies are focused on unraveling the underlying pathophysiological mechanisms that govern these risk factors, with the main goal of identifying novel biomarkers and therapeutic targets to prevent the onset of CVD in the population. In recent decades, genome-wide association studies (GWAS) have linked the 8q24 locus containing the TRIB1 gene to various cardiometabolic traits in humans, such as plasma triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), total cholesterol (TC), adiponectin, and HbA1c levels. Emerging research has investigated the role of Trib1 (Tribbles homolog 1) in regulating plasma lipid levels, inflammation, and insulin signaling, opening new avenues for the potential therapeutic role of Trib1 in CVD risk assessment. Accordingly, this review aims to explore the crucial role of Trib1 as a therapeutic biomarker in CVDs, with a focus on its association with lipid metabolism, atherosclerosis, obesity and diabetes analyzing in vitro and in vivo studies and offering insights into its underlying molecular mechanisms.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953461","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}

{"title":"Multi-therapeutic strategy targeting Akt-mTOR and FoxO1 pathway to counteract skeletal muscle atrophy consecutive to hypoxia.","authors":"Samir Bensaid, Fabre Claudine, Amir Yahya Rajaei, Charlotte Claeyssen, Frédéric N Daussin, Caroline Cieniewski-Bernard","doi":"10.1152/ajpcell.00851.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00851.2024","url":null,"abstract":"<p><p>Chronic oxygen deprivation, whether due to high altitude or certain diseases as cardiorespiratory pathologies, leads to muscle atrophy. To limit muscle loss, counteracting programs rely on only one therapeutic approach: return to sea level altitude, physical activity or nutritional supplementation; however, little effects are noticed on muscle mass of subjects presenting a severe hypoxemia. We hypothesized that the combination of several treatments (electrical stimulation and/or nutritional supplementation and/or oxygenation) would improve anabolic responses, counteracting thus efficiently hypoxia-induced muscle atrophy. In C2C12 myotubes submitted to hypoxia, we aim at testing several treatments based on the combination of electrical stimulation, amino acids supplementation and/or an oxygenation period. In comparison to untreated muscle cells under hypoxia, all treatments had an anabolic impact on myotubes morphology (myogenic fusion index, diameter and density of myotubes), on proteosynthesis pathway (Akt, mTOR, GSK-3β, 4E-BP1 and P70S6K), on proteolysis pathway (FoxO1, myostatin, ubiquitin-proteasome system) and on hypoxia marker (REDD1) protein level. Electrical stimulation alone resulted in hyperphosphorylation of Akt and FoxO1 while its combination with amino acids supplementation alleviated atrophy exemplified by fusion index and myotubes diameter increase up to 48 hours post-application. Electrical stimulation followed by a period of oxygenation of hypoxic muscle cells strongly increased the activation status of 4E-BP1 and P70S6K. Lastly, simultaneous application of all treatments (electrical stimulation, amino acids supplementation and oxygenation) was the only condition resulted in activation of mTOR concomitantly to myostatin level decrease. These results support that the activation of the mTOR pathway through the combined application of electrical stimulation and BCAAs is strongly influenced by oxygen availability, and that oxygen plays a critical role in optimizing protein synthesis pathway in hypoxic skeletal muscle cells.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964665","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}

{"title":"PCP protein Prickle 1 regulates Sertoli cell and testis function via cytoskeletal organization through the recruitment of multiple regulatory proteins.","authors":"Lingling Wang, Tiao Bu, Sheng Gao, Damin Yun, Hao Chen, C Yan Cheng, Fei Sun","doi":"10.1152/ajpcell.00861.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00861.2024","url":null,"abstract":"<p><p>Prickle 1, an ortholog found in <i>Drosophila</i>, was localized at the Sertoli cell-spermatid interface consistent with its role of supporting the Vangl2 planar cell polarity (PCP), is an integral membrane protein that creates the PCP protein complex of Vangl2 (Van Gogh-like 2)/Prickle1. Together with the asymmetrically localized transmembrane protein Frizzled (Fzd) and its unique adaptor proteins Disheveled (Dvl) and Inversin (Inv), Vangl2/Prickle1 and Fzd/Dvl/Inv are the two heterodimeric interacting PCP proteins between Sertoli cells and condensed spermatids to confer spermatid PCP across the plane of the seminiferous epithelium. Our initial intention was to examine if the distribution and expression of Prickle1 using a primary Sertoli cell in vitro model and Sprague-Dawley rats in vivo would mimic much of the earlier reported findings of Vangl2. Unexpectedly, these findings indicated that Prickle1 supported the PCP protein Vangl2, however, Prickle1 is also a multifunctional protein. First, Prickle1 knockdown (KD) by RNAi impeded Sertoli cell TJ-function by perturbing the distribution of the BTB-associated proteins at the cell-cell interface, through disruption of the microtubule (MT) and actin cytoskeletal organization including their respective polymerization (and/or bundling) capability. Second, these findings were reproduced using an in vivo model of RNAi by KD of Prickle 1 in the testis. Third, using Co-Immunoprecipitation (Co-IP), Prickle 1 was found to interact with a host of adaptor proteins crucial to support PCP including Dvl, but also regulatory cytoskeletal proteins of MT and actin networks, including RhoA, Arp3, Cdc42, ZO-1, and ß-catenin by IP-MS (Immunoprecipitation-Mass Spectrometry) using the String Protein Interaction Tool.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956569","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}

{"title":"Molecular determinants of HCO₃^- and cation transport in the human cation-dependent Cl^-/HCO₃^- exchanger AE4.","authors":"Marcelo A Catalán, Lisandra Flores-Aldama, Fernanda Fernández, Daniel Bustos, Natalia Apablaza, Ailen Hidalgo, Yuliet Mazola, Ella Matamala, Li Yo Kao, Ira Kurtz, Carlos Spichiger, José Sarmiento, Sebastian Brauchi, Wendy González, Leandro Zúñiga, Gaspar Peña-Münzenmayer","doi":"10.1152/ajpcell.00346.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00346.2024","url":null,"abstract":"<p><p>The HCO₃^- transporter AE4 (SLC4A9) plays a role in NaCl reabsorption and pH sensing in the kidney, and Cl^--dependent fluid secretion in salivary glands. Sharing functional features with other Cl^-/HCO₃^- exchangers and Na⁺-HCO₃^- co-transporters, it has been proposed that AE4 mediates Cl^-/cation- HCO₃^- exchange. Our sequence alignments and molecular dynamics (MD) analysis showed that three residues, reported as critical for transport activity in other SLC4 transporters, are conserved in AE4, suggesting similarities in their ion transport mechanism. Site-directed mutagenesis and further functional experiments showed that two out of the three conserved residues (D709 and T448) are functionally relevant but in contrast to other SLC4 transporters, where transport was almost completely abolished, AE4 mutants conserved about 50% of transport activity. Additionally, alanine scanning showed that S446A and T756A decreased transport by nearly 30%. Consistent with an additive effect of mutations at positions T756 and T448, the double mutant T756A-T448I completely abolished transport in the presence of extracellular Na⁺, but interestingly, exhibited anion transporter activity in the presence of K⁺ as the main extracellular cation. MD simulations revealed that the HCO₃^- and cation coordination site is at the interface between the transmembrane segments TM3-TM10. The interaction network was importantly disrupted in the double mutant in the presence of Na⁺, but it is partially conserved in the presence of K⁺, suggesting differences in the cation coordination. In summary, we identified the putative cation coordination site of AE4 and the critical functional role of residues T756 and T448 in its transport cycle.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966229","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}

{"title":"Single-cell transcriptomic analysis reveals alterations to cellular dynamics and paracrine signalling in radiation-induced muscle pathology.","authors":"Nicolás Collao, Emma B Johannsen, Jesper Just, Michael De Lisio","doi":"10.1152/ajpcell.00115.2025","DOIUrl":"https://doi.org/10.1152/ajpcell.00115.2025","url":null,"abstract":"<p><p>Radiation therapy causes long-term skeletal muscle atrophy and fibrosis in juvenile cancer survivors. The mechanisms responsible for the skeletal muscle late effects of radiation therapy are not well-understood and have prevented the development of effective treatments. Using single-cell RNA sequencing (scRNA-seq), we characterize cellular dynamics and communication in a murine model of therapeutic radiation at 24-hours and 56-days post-irradiation (post-IR). We detected changes in muscle stem (satellite) cells (MuSCs) characterized by an acute preservation of committed MuSCs and long-term relative depletion of deep quiescent MuSCs. A conserved senescence <i>Cdkn1a</i> signature was observed in all muscle-resident cells post-IR. Genes related to fibroblast proliferation were up-regulated and a fibrotic and senescent transcriptome persisted in Fibro-adipogenic progenitors (FAPs) post-IR. Intercellular communication analysis revealed FAPs as the primary contributor of extracellular matrix (ECM) and target of monocyte/macrophage-derived TGF-β signalling post-IR through TGF-βR2 on FAPs. Together, our findings provide insights into the potential mechanisms and intercellular communication responsible for radiation-induced muscle atrophy and fibrosis.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959998","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}

{"title":"Enteroendocrine cells regulate intestinal barrier permeability.","authors":"Jennifer G Nwako, Sparsh D Patel, Taevon J Roach, Saanvi R Gupte, Samara G Williams, Anne Marie Riedman, Heather A McCauley","doi":"10.1152/ajpcell.01077.2024","DOIUrl":"10.1152/ajpcell.01077.2024","url":null,"abstract":"<p><p>The intestinal epithelial barrier is essential for nutrient absorption and protection against ingested pathogens and foreign substances. Barrier integrity is maintained by tight junctions, which are sensitive to inflammatory signals, thus creating a feed-forward loop with an increasingly permeable barrier that further drives inflammation and is the hallmark of inflammatory bowel disease. There are currently no therapeutic strategies to improve the intestinal epithelial barrier. We hypothesized that enteroendocrine cells may play an unappreciated role in maintaining barrier integrity. To test this hypothesis, we seeded human intestinal enteroids with genetic loss of enteroendocrine cells on Transwell filters and evaluated transepithelial electrical resistance, paracellular permeability, and the localization and abundance of junctional proteins. We found that enteroendocrine cells were required to maintain a healthy barrier in crypt-like \"stem\" and villus-like differentiated cultures. In addition, exogenous supplementation of enteroendocrine-deficient cultures with the hormones peptide tyrosine-tyrosine (PYY), and the somatostatin analog octreotide was sufficient to rescue many aspects of this barrier defect both at baseline and in the presence of the inflammatory cytokine tumor necrosis factor. Surprisingly, these improvements in barrier function occurred largely independently of changes in protein abundance of junctional proteins zona occludens 1, occludin, and claudin-2. These findings support a novel role for enteroendocrine cells in augmenting epithelial barrier function in the presence of inflammatory stimuli and present an opportunity for developing therapies to improve the intestinal barrier.<b>NEW & NOTEWORTHY</b> There are no therapies that directly improve the permeability of the intestinal epithelial barrier. This work uses a human intestinal epithelial model system to demonstrate that sensory enteroendocrine cells are necessary for healthy barrier function and that two of their secreted products, peptide YY and somatostatin, are sufficient to improve barrier function at homeostasis and in the presence of inflammatory cytokines. This could provide novel treatments for strengthening the epithelial barrier in human gastrointestinal disease.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1501-C1508"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646946","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}

{"title":"The long road to Ithaca: a physiologist's journey.","authors":"Sadis Matalon","doi":"10.1152/ajpcell.00030.2025","DOIUrl":"10.1152/ajpcell.00030.2025","url":null,"abstract":"<p><p>It was an honor to be asked to deliver the Walter B. Cannon Lecture during the 2024 American Physiological Summit meeting. Dr. Cannon served as president of the American Physiological Society from 1914-1916. He coined the term \"fight or flight\" to describe an animal's response to threats and the concept of Homeostasis. He was the consummate physician-scientist, an outstanding mentor and teacher, a prolific writer, and a humanitarian. The title of my lecture is based on a poem entitled \"Ithaca,\" written by the Greek poet C. P. Cavafy, who recounts the 10 yr travels of Ulysses, from Troy to his home, Ithaca. Odysseus had to overcome many obstacles to survive this long journey. Like Odysseus, I encountered myriad of professional and health problems. But, I also have experienced the thrill of contributing to scientific knowledge, the satisfaction of watching my mentees develop into independent scientists, the excitement of teaching respiration physiology to medical and professional students, and the pleasure of being of service to my discipline by serving as Editor of the American Journal of Physiology-Lung Cellular and Molecular Physiology and of Physiological Reviews. During my career, I have been interested in identifying the basic mechanisms by which oxidant gases and pathogens damage the blood gas barrier resulting in acute and chronic lung injury. In this brief review, I summarize the results of current studies implicating free heme as a major mediator of acute lung injury and our efforts to develop recombinant forms of human hemopexin, as a countermeasure.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1526-C1534"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490526","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}

{"title":"A novel lncRNA ABCE1-5 regulates pulmonary fibrosis by targeting KRT14.","authors":"Shuwei Gao, Yanqiu Wei, Chen Li, Bingbing Xie, Xinran Zhang, Ye Cui, Huaping Dai","doi":"10.1152/ajpcell.00374.2024","DOIUrl":"10.1152/ajpcell.00374.2024","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive and degenerative interstitial lung disease characterized by complex etiology, unclear pathogenesis, and high mortality. Long noncoding RNAs (lncRNAs) have been identified as key regulators in modulating the initiation, maintenance, and progression of pulmonary fibrosis. However, the precise pathological mechanisms through which lncRNAs are involved in IPF remain limited and require further elucidation. A novel lncABCE1-5 was identified as significantly decreased by an ncRNA microarray analysis in our eight IPF lung samples compared with three donor tissues and validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in clinical lung samples. To investigate the biological function of ABCE1-5, we performed loss- and gain-of-function experiments in vitro and in vivo. LncABCE1-5 silencing promoted A549 cell migration and A549 and bronchial epithelial cell line (BEAS-2B) cell apoptosis while enhancing the expression of proteins associated with extracellular matrix deposition, whereas overexpression of ABCE1-5 partially attenuated transforming growth factor-beta (TGF-β)-induced fibrogenesis. Forced ABCE1-5 expression by intratracheal injection of adeno-associated virus 6 revealing the antifibrotic effect of ABCE1-5 in bleomycin (BLM)-treated mice. Mechanistically, RNA pull-down (RPD)-mass spectrometry and RNA immunoprecipitation assay demonstrated that ABCE1-5 directly binds to keratin14 (krt14) sequences, potentially impeding its expression by perturbing mRNA stability. Furthermore, decreased ABCE1-5 levels can promote krt14 expression and enhance the phosphorylation of both mTOR and Akt; overexpression of ABCE1-5 in BLM mouse lung tissue significantly attenuated the elevated levels of p-mTOR and p-AKT. Knockdown of krt14 reversed the activation of mTOR signaling mediated by ABCE1-5 silencing. Collectively, the downregulation of ABCE1-5 mediated krt14 activation, thereby activating mTOR/AKT signaling, to facilitate pulmonary fibrosis progression in IPF.<b>NEW & NOTEWORTHY</b> In the present study, our data first reveal that a novel lncRNA ABCE1-5 could inhibit pulmonary fibrosis through interacting with krt14 and negative regulation of its expression, and indicated ABCE1-5 also regulates the phosphorylation of mTOR and Akt, thus acting on extracellular matrix remodeling in lung fibrosis procession. These results suggest that novel molecules within the ABCE1-5-krt14-mTOR axis may serve as potential candidates for clinical application in IPF.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1487-C1500"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668864","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}

{"title":"Recent advances in synthetic Notch receptors for biomedical application.","authors":"Luyao Song, Qinmeng Zhang, Hairu Sui, Chenlu Gao, Zhiwei Jiang","doi":"10.1152/ajpcell.00659.2024","DOIUrl":"10.1152/ajpcell.00659.2024","url":null,"abstract":"<p><p>The synthetic Notch receptor has emerged as a potent tool for precisely modulating cellular functions. It constitutes a receptor system rooted in the Notch signaling pathway. SynNotch receptors, coupled with downstream transcription programs, hold promise for organoid and three-dimensional (3-D) tissue construction. In addition, it enables the tracking and visualization of intercellular communication. Moreover, engineering SynNotch cells to carry specific receptors markedly enhances the efficacy and safety of immunotherapy. This review delineates the subdomains and tunable mechanisms of SynNotch, summarizing four core modes of combinatorial multiplexing potentially pivotal for regulating SynNotch cell functions. Furthermore, this review summarizes the multifaceted applications, advantages, and limitations of SynNotch, offering fresh insights into its future biomedical utilization.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1473-C1486"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708194","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}

{"title":"Resistance exercise and mechanical overload upregulate vimentin for skeletal muscle remodeling.","authors":"Joshua S Godwin, J Max Michel, Cleiton A Libardi, Andreas N Kavazis, Christopher S Fry, Andrew D Frugé, Mariah McCashland, Ivan J Vechetti, John J McCarthy, C Brooks Mobley, Michael D Roberts","doi":"10.1152/ajpcell.01028.2024","DOIUrl":"10.1152/ajpcell.01028.2024","url":null,"abstract":"<p><p>We adopted a proteomic and follow-through approach to investigate how mechanical overload (MOV) potentially affects novel targets in skeletal muscle, and how a perturbation in this response could potentially affect the adaptive response. First, we determined that 10 wk of resistance training in 15 college-aged females increased sarcolemmal-associated protein content (+10.1%, <i>P</i> < 0.05). Sarcolemmal protein isolates were then queried using mass spectrometry-based proteomics, ∼10% (38/387) of proteins putatively associated with the sarcolemma or extracellular matrix (ECM) were upregulated (>1.5-fold, <i>P</i> < 0.05), and one target (intermediate filament vimentin; VIM) warranted further investigation due to its correlation to myofiber hypertrophy (<i>r</i> = 0.652, <i>P</i> = 0.009). VIM expression was then examined in 4-mo-old C57BL/6J mice following 10 and 20 days of plantaris MOV via synergist ablation. Relative to Sham (control) mice, VIM mRNA and protein content was significantly higher in MOV mice, and immunohistochemistry indicated that VIM predominantly resided in the ECM. MOV experiments were replicated in Pax7-DTA (satellite cell depleted) mice, which reduced VIM in the ECM by ∼74%. A third MOV experiment was performed in C57BL/6 mice intramuscularly injected with either AAV9-scrambled (control) or AAV9-VIM-shRNA. Although VIM-shRNA mice possessed lower VIM in the ECM (∼45%), plantaris masses in response to MOV were similar between groups. However, VIM-shRNA mice possessed smaller and more centrally nucleated MyHC_emb-positive fibers in response to MOV. In summary, skeletal muscle VIM appears to be enriched in the ECM following MOV, satellite cells may regulate its expression, and a disruption in expression during MOV leads to an excessive regenerative phenotype.<b>NEW & NOTEWORTHY</b> Our highly integrative approach suggests that skeletal muscle vimentin seems to function as a mechanosensitive protein that becomes enriched in the extracellular matrix following MOV. Satellite cells may play a role in regulating their expression, and an exaggerated regenerative response occurs when vimentin expression becomes dysregulated during mechanical overload. Although these data implicate vimentin in aiding with tissue remodeling following MOV, more data are needed to determine the functional ramifications of VIM response deficiencies.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1509-C1525"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770849","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}