American journal of physiology. Cell physiology最新文献

{"title":"No detectable loss of myonuclei from human muscle fibers after 6 wk of immobilization following an Achilles tendon rupture.","authors":"Oscar Horwath, Kristoffer Toldnes Cumming, Einar Eftestøl, Björn Ekblom, Paul Ackermann, Truls Raastad, Kristian Gundersen, Niklas Psilander","doi":"10.1152/ajpcell.00692.2024","DOIUrl":"10.1152/ajpcell.00692.2024","url":null,"abstract":"<p><p>Muscle disuse has rapid and debilitating effects on muscle mass and overall health, making it an important issue from both scientific and clinical perspectives. However, the myocellular adaptations to muscle disuse are not yet fully understood, particularly those related to the myonuclear permanence hypothesis. Therefore, in this study, we assessed fiber size, number of myonuclei, satellite cells, and capillaries in human gastrocnemius muscle after a period of immobilization following an Achilles tendon rupture. Six physically active patients (5 males/1 female, 43 ± 15 yr) were recruited to participate after sustaining an acute unilateral Achilles tendon rupture. Muscle biopsies were obtained from the lateral part of the gastrocnemius before and after 6 wk of immobilization using a plaster cast and orthosis. Muscle fiber characteristics were analyzed in tissue cross-sections and isolated single fibers using immunofluorescence and high-resolution microscopy. Immobilization did not change muscle fiber type composition nor cross-sectional area of type I or type II fibers, but muscle fiber volume tended to decline by 13% (<i>P</i> = 0.077). After immobilization, the volume per myonucleus was significantly reduced by 20% (<i>P</i> = 0.008). Myonuclei were not lost in response to immobilization but tended to increase in single fibers and type II fibers. No significant changes were observed for satellite cells or capillaries. Myonuclei were not lost in the gastrocnemius muscle after a prolonged period of immobilization, which may provide support to the myonuclear permanence hypothesis in human muscle. Capillaries remained stable throughout the immobilization period, whereas the response was variable for satellite cells, particularly in type II fibers.<b>NEW & NOTEWORTHY</b> The impact of prolonged immobilization on muscle fiber characteristics is difficult to study in humans and therefore remains poorly understood. We analyzed cross-sections and single fibers from gastrocnemius before and after 6 wk of immobilization due to an Achilles tendon rupture. Our data suggest that myonuclei are not lost in response to such stimuli, thus lending support to the hypothesis of myonuclear permanency in human muscle.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C20-C26"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638537","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":"Role of myofiber-specific FoxP1 in pancreatic cancer-induced muscle wasting.","authors":"Martin M Schonk, Jeremy B Ducharme, Daria Neyroud, Rachel L Nosacka, Haley O Tucker, Sarah M Judge, Andrew R Judge","doi":"10.1152/ajpcell.00701.2024","DOIUrl":"10.1152/ajpcell.00701.2024","url":null,"abstract":"<p><p>Cancer cachexia affects up to 80% of patients with cancer and results in reduced quality of life and survival. We previously demonstrated that the transcriptional repressor Forkhead box P1 (FoxP1) is upregulated in the skeletal muscle of cachectic mice and people with cancer, and when overexpressed in skeletal muscle, it is sufficient to induce pathological features characteristic of cachexia. However, the role of myofiber-derived FoxP1 in both normal muscle physiology and cancer-induced muscle wasting remains largely unexplored. To address this gap, we generated a conditional mouse line with myofiber-specific ablation of FoxP1 (FoxP1^SkmKO) and found that in cancer-free mice, deletion of FoxP1 in skeletal myofibers resulted in increased myofiber size in both males and females, with a significant increase in muscle mass in males. In response to murine KPC pancreatic tumor burden, we found that myofiber-derived FoxP1 mediates cancer-induced muscle wasting and diaphragm muscle weakness in male but not female mice. In summary, our findings identify myofiber-specific FoxP1 as a negative regulator of skeletal muscle with sex-specific differences in the context of cancer.<b>NEW & NOTEWORTHY</b> Here we identify myofiber-derived FoxP1 as a negative regulator of skeletal muscle with sex-specific effects in cancer. Under cancer-free conditions, FoxP1 knockout increased myofiber size in male and female mice. However, in response to pancreatic cancer, FoxP1 myofiber-specific deletion attenuated muscle wasting and weakness in males but not females. This highlights the need to consider sexual dimorphism in cancer-induced muscle pathologies and provides evidence suggesting that targeting FoxP1 could help mitigate these effects in males.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1-C8"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612360","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":"β3-adrenergic agonist counters oxidative stress and Na⁺-K⁺ pump inhibitory S-glutathionylation of placental cells: implications for preeclampsia.","authors":"Chia-Chi Liu, Yunjia Zhang, Yeon Jae Kim, Elisha J Hamilton, Bei Xu, Jane Limas, Sharon A McCracken, Jonathan M Morris, Angela Makris, Annemarie Hennessy, Helge H Rasmussen","doi":"10.1152/ajpcell.00379.2024","DOIUrl":"10.1152/ajpcell.00379.2024","url":null,"abstract":"<p><p>Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by Na⁺-K⁺ pump inhibition and S-glutathionylation of its β1 subunit (GSS-β1), a modification that inhibits the pump. β3-adrenergic receptor (β3-AR) agonists can reverse GSS-β1. We examined the effects of the agonist CL316,243 on GSS-β1 and sources of H/R-induced oxidative stress in immortalized first-trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal-term pregnancies. H/R increased GSS-β1 and, reflecting compromised α1/β1 subunit interaction, reduced α1/β1 pump subunit coimmunoprecipitation. H/R increased p47<i>^phox</i>/p22<i>^phox</i> NADPH oxidase subunit coimmunoprecipitation, reflecting membrane translocation of cytosolic p47<i>^phox</i> that is needed to activate NADPH oxidase. Fluorescence of O₂^•--sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples nitric oxide synthesis toward the synthesis of O₂^•- and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor α increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-β1 and decreases of α1/β1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release, and restored trophoblast integration in endothelial cell networks. H/R-induced GSS-β1, α1/β1 subunit coimmunoprecipitation, and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a β3-AR agonist counters key pathophysiological features of preeclampsia in vitro. β3 agonists already in human use for another purpose are potential candidates for repurposing to treat preeclampsia.<b>NEW & NOTEWORTHY</b> H/R-induced oxidative stress and deficient NO-dependent placentation are features of preeclampsia, yet nonspecific antioxidants and NO donors are ineffective. Here, activation of the microdomain-confined signaling pathway with an agonist for the eNOS-coupled β3-AR eliminates inhibitory glutathionylation of the Na⁺-K⁺ pump's β1 subunit, uncoupling of eNOS, and activation of NADPH oxidase that are sources of H/R-induced oxidative stress. The agonist also eliminates H/R-induced inhibition of trophoblast migration and their integration into an endothelial network.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C27-C39"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567390","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":"Histone lactylation-mediated overexpression of RASD2 promotes endometriosis progression via upregulating the SUMOylation of CTPS1.","authors":"Ziwei Wang, Yanhong Mao, Zihan Wang, Shuwei Li, Zhidan Hong, Rong Zhou, Shaoyuan Xu, Yao Xiong, Yuanzhen Zhang","doi":"10.1152/ajpcell.00493.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00493.2024","url":null,"abstract":"<p><p><b>Background:</b> Histone lactylation is crucial in a variety of physiopathological processes, however, the function and mechanism of histone lactylation in endometriosis remain poorly understood. Therefore, the objective of this investigation was to illuminate the function and mechanism of histone lactylation in endometriosis. <b>Methods:</b> Immunohistochemistry was used to investigate the expression of histone lactylation. Cell Counting Kit-8 assay (CCK8), Transwell assay and endometriosis mouse models were used to investigate the effects of histone lactylation in vitro and in vivo. Transcriptomics and Immunoprecipitation-Mass Spectrometry (IP-MS), Western Blot, Co-Immunoprecipitation (Co-IP), quantitative reverse transcription polymerase chain reaction (qRT-PCR) and chromatin immunoprecipitation-qPCR (ChIP-qPCR) were used to explore the intrinsic mechanisms. <b>Results:</b> In this study, we found that histone lactylation was upregulated in endometriosis and could promote endometriosis progression both in vivo and in vitro. Mechanistically, histone lactylation H3K18la promoted the transcription of Ras homolog enriched in striatum (RASD2), and RASD2, in turn, increased the stability of CTP synthase 1 (CTPS1) by promoting the SUMOylation and inhibiting the ubiquitination of CTPS1, thereby promoting endometriosis progression. <b>Conclusion:</b> Overall, our findings indicated that histone lactylation could promote the progression of endometriosis through the RASD2/CTPS1 axis. This investigation uncovered a novel mechanism and identified prospective targets for endometriosis diagnosis and therapy.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821823","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":"METTL14 promotes ferroptosis in smooth muscle cells during thoracic aortic aneurysm by stabilizing the m⁶A modification of ACSL4.","authors":"Wenjun Wang, Jiayi Chen, Songqing Lai, Ruiyuan Zeng, Ming Fang, Li Wan, Yiying Li","doi":"10.1152/ajpcell.00577.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00577.2024","url":null,"abstract":"<p><p>Thoracic aortic aneurysm (TAA) is a vascular disease associated with high mortality rates. Ferroptosis has been shown to mediate the transformation of vascular smooth muscle cells (VSMCs). However, the regulatory mechanisms by which ferroptosis influences TAA remain unclear. In this study, we induced TAA mouse models using angiotensin II (Ang II) and evaluated the impact of ferroptosis on the pathological changes observed in TAA mice, employing liproxstatin-1 as a treatment. Additionally, we assessed the regulatory effect of METTL14 on the ferroptosis of VSMCs after treating them with ferroptosis activator (IKE). RNA binding protein immunoprecipitation (RIP) and RNA pull-down assays were conducted to investigate the interaction between ACSL4 mRNA and the proteins METTL14 or IGF2BP2. The results indicated that the level of ferroptosis was elevated in the thoracic aorta of TAA mice, and METTL14 was upregulated in TAA models and IKE-induced VSMCs. Knockdown of METTL14 was found to inhibit the progression of TAA by reducing the ferroptosis of VSMCs. Furthermore, IGF2BP2 recognized METTL14-modified ACSL4 mRNA and regulated its stability, thereby mediating the ferroptosis of VSMCs. Collectively, the effects of METTL14 on VSMC ferroptosis present therapeutic potential for the treatment of TAA.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821824","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":"RFC4 confers radioresistance of esophagus squamous cell carcinoma through regulating DNA damage response.","authors":"Tao Yang, Yue Fan, Guang Bai, Yinpeng Huang","doi":"10.1152/ajpcell.00533.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00533.2024","url":null,"abstract":"<p><p>Radioresistance in esophageal squamous cell carcinoma (ESCC) is a critical factor leading to treatment failure and recurrence, yet its underlying molecular mechanisms remain unclear. This study aimed to investigate the role of Replication Factor C4 (RFC4) in ESCC radioresistance and to explore the underlying mechanisms. We utilized online bioinformatics tools to analyze the properties, functions, and prognostic significance of RFC4 in ESCC. We established cell lines with varying RFC4 expression levels and subjected them to radiation exposure. RFC4 expression was assessed using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunoblotting. Cell proliferation was evaluated with MTT, EdU, and colony formation assays. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting and immunofluorescence were used to study the impact of RFC4 on the DNA damage response in ESCC cells. A xenograft mouse model was employed to assess tumor growth <i>in vivo</i>. RFC4 expression was significantly upregulated in ESCC tissues and cells, particularly in radioresistant cases. Functional experiments revealed that RFC4 promotes cell proliferation, inhibits apoptosis, induces cell cycle arrest, and mitigates radiation-induced DNA damage responses. Mechanistically, RFC4-mediated radioresistance in ESCC may involve the inactivation of the p53 signaling pathway. In animal studies, RFC4 knockdown, either alone or in combination with radiation therapy, effectively suppressed the growth of xenograft tumors. These findings highlight the potential of targeting RFC4 to overcome radioresistance by modulating the DNA damage response in ESCC, offering promising therapeutic avenues for ESCC patients.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821826","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":"Sulforaphane treatment mimics contractile activity-induced mitochondrial adaptations in muscle myotubes.","authors":"Sabrina Champsi, David A Hood","doi":"10.1152/ajpcell.00669.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00669.2024","url":null,"abstract":"<p><p>Mitochondria are metabolic hubs that govern skeletal muscle health. While exercise has been established as a powerful inducer of quality control processes that ultimately enhance mitochondrial function, there are currently limited pharmaceutical interventions available that emulate exercise-induced mitochondrial adaptations. To investigate a novel candidate for this role, we examined Sulforaphane (SFN), a naturally occurring compound found in cruciferous vegetables. SFN has been documented as a potent antioxidant inducer through its activation of the nuclear factor erythroid 2-related factor 2 (Nrf-2) antioxidant response pathway. However, its effects on muscle health have been underexplored. To investigate the interplay between chronic exercise and SFN, C2C12 myotubes were electrically stimulated to model chronic contractile activity (CCA) in the presence or absence of SFN. SFN promoted Nrf-2 nuclear translocation, enhanced mitochondrial respiration, and upregulated key antioxidant proteins including catalase and glutathione reductase. These adaptations were accompanied by reductions in cellular and mitochondrial ROS emission. Signaling towards biogenesis was enhanced, demonstrated by increases in mitochondrial transcription factor A (TFAM), Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α nuclear translocation, PGC-1α promoter activity, mitochondrial content, and organelle branching, suggestive of a larger, more interconnected mitochondrial pool. These mitochondrial adaptations were accompanied by an increase in lysosomal proteins, suggesting coordinated regulation. There was no difference in mitochondrial and antioxidant-related proteins between CCA and non-CCA SFN-treated cells. Our data suggests that SFN activates signaling cascades that are common to those produced by contractile activity, indicating that SFN-centered therapeutic strategies may improve the mitochondrial phenotype in skeletal muscle.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821827","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":"Prevention of Cardiovascular Disease in Women with Type 2 Diabetes: The Role of Incretin Mimetics and Sodium-Glucose Cotransporter-2 Inhibitors.","authors":"Eiman Ibrahim, Mya Burken, Guido Lastra, Camila Manrique-Acevedo","doi":"10.1152/ajpcell.00765.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00765.2024","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is the leading cause of death among individuals with type 2 diabetes (T2D), with women experiencing a disproportionate risk of events compared to men. Women have an amplified burden of cardiovascular risk factors once T2D is diagnosed. Incretin mimetics now play a central role in managing cardiovascular risk by improving glycemic control, promoting weight loss, and potentially exerting direct cardioprotective effects. Similarly, sodium-glucose cotransporter 2 inhibitors contribute to CVD prevention through various non-glucose lowering mechanisms. Both classes of medications are integral to personalized treatment strategies aimed at addressing the heightened cardiovascular risk faced by women with diabetes. This mini-review addresses possible mechanisms underlying the increased cardiovascular risk and explores the role of incretin mimetics and SGLT2 inhibitors in mitigating CVD in women with T2D. Emphasizing personalized and sex-specific approaches in diabetes care is crucial for optimizing treatment outcomes and improving cardiovascular health.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821825","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":"Role of versican in extracellular matrix formation: analysis in 3D culture.","authors":"Nushrat Jahan, Shamima Islam, Karnan Sivasundaram, Akinobu Ota, Munekazu Naito, Junpei Kuroda, Hideto Watanabe","doi":"10.1152/ajpcell.00495.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00495.2024","url":null,"abstract":"<p><p>Three-dimensional cell culture creates an environment that allows cells to grow and interact with the surrounding extracellular framework. Versican plays a pivotal role in forming the provisional matrix, but it is still unclear how this proteoglycan affects the formation of the extracellular matrix. Here, we established a three-dimensional culture system using fibrin gel, which enables a long-term culture up to a month. With this system, we characterized fibroblasts obtained from the newborn knock-in homozygotes, termed R/R, expressing ADAMTS-resistant versican and wild-type mice. R/R fibroblasts showed higher levels of versican deposition than wild-type, demonstrating that the initial ADAMTS-cleavage site is involved in versican turnover. These fibroblasts exhibited faster proliferation and myofibroblastic differentiation, concomitant with higher levels of TGFβ-signaling. R/R fibroblast culture had higher deposition levels of fibronectin, type I and V collagens, and fibrillin-1, especially at the late stages of culture. These results suggest that versican expressed by dermal fibroblasts facilitates the extracellular matrix formation, at least by affecting fibroblast behavior.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798695","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":"Knockdown of KLF6 ameliorates myocardial infarction by regulating autophagy via transcriptional regulation of PTTG1.","authors":"Yixin Chen, Qian Zhao, Tengfei Wu, Feifei Sun, Weineng Fu","doi":"10.1152/ajpcell.00191.2024","DOIUrl":"https://doi.org/10.1152/ajpcell.00191.2024","url":null,"abstract":"<p><p>Krüppel-like factor 6 (KLF6) knockdown provides protection against kidney ischemia/reperfusion (I/R) injury and ischemic stroke. However, it is unclear whether it plays a role in myocardial infarction (MI) remains unknown. Here, the expression of KLF6 was analyzed using the GEO database and determined in patients with MI. The impact of KLF6 knockdown was further confirmed in <i>in vivo</i> and ><i>in vitro</i> models of MI. The interaction between KLF6 and PTTG1 was also evaluated. According to the GEO database, KLF6 expression was found to be upregulated in mouse hearts after MI compared to sham-operated mice. The upregulation of KLF6 in hearts from mice post-MI and in patients with MI was confirmed. KLF6 knockdown was found to alleviate myocardial injury, diminish infarct size, and suppress apoptosis and autophagy in mice with MI. Additionally, inactivation of the AMPK/mTOR signaling was observed after KLF6 knockdown in mice with MI. In an <i>in vitro</i> model of MI, knockdown of KLF6 increased cell survival and inhibited autophagy through the AMPK/mTOR pathway. Additionally, KLF6 interacted with the promoter of PTTG1 and negatively regulated its expression. Knockdown of PTTG1 abolished the function of KLF6 knockdown <i>in vitro</i>. This study demonstrates the protective effect of KLF6 knockdown against MI, which is attributed to the elevation of PTTG1 expression and inhibition of the AMPK/mTOR pathway. These findings provide a novel insight into MI treatment.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798685","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}