JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"ANXA1-Derived Peptide Increases Melanoma Cell Sensitivity to Vemurafenib by Downregulating EphA2","authors":"Juan Feng,&nbsp;Xiao-Pu Huang,&nbsp;Ming Zhang,&nbsp;Wei Huang,&nbsp;Shan-Shan Lu,&nbsp;Zhi-Qiang Xiao,&nbsp;Zhi-Hai Xie,&nbsp;Hong Yi","doi":"10.1111/jcmm.71310","DOIUrl":"https://doi.org/10.1111/jcmm.71310","url":null,"abstract":"<p>Vemurafenib (VEM) is a BRAF inhibitor that improves the prognosis of melanoma, but acquired resistance represents a key limitation to its clinical efficacy. This study investigated the potential of A11, an Annexin A1 (ANXA1)-derived peptide, to enhance VEM efficacy in both VEM-sensitive and VEM-resistant melanoma cells. We evaluated the effects of A11 in melanoma through in vitro assays (including MTT, clonogenic survival, apoptosis, and cell cycle analysis) and in vivo xenograft models in nude mice. Furthermore, we mechanistically interrogated A11-mediated suppression of EphA2 expression and the downstream pS897-EphA2/AKT/ERK signalling pathway in resistant and parental cell lines via Western blotting and immunohistochemistry (IHC). Critically, our study demonstrates that A11 inhibits melanoma cell proliferation and reverses VEM resistance through EphA2 downregulation, consequently ablating this oncogenic pathway. This research highlights the promising application value of A11 in improving the efficacy of VEM treatment in melanoma, particularly in VEM-resistant melanoma.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the New Trick for Epigenetic Drug: Radiation Enhancement of Prostate Cancer by the EZH2 Inhibitor Tazemetostat","authors":"Tian-Qi Du,&nbsp;Yuhong Ou,&nbsp;Rui-Ji Liu,&nbsp;Yi Feng,&nbsp;Yaxun Li,&nbsp;Gang Chen,&nbsp;Xingyu Wu","doi":"10.1111/jcmm.71330","DOIUrl":"https://doi.org/10.1111/jcmm.71330","url":null,"abstract":"<p>The enhancer of zeste homologue 2 inhibitor (EZH2i) Tazemetostat (EPZ-6438) has demonstrated antitumour efficacy in various malignancies. This study aims to evaluate its radiosensitising potential and underlying mechanisms in prostate cancer (PCa). In vitro functional assays, including wound healing, Transwell invasion, EdU proliferation, flow cytometry, and Western blotting, were employed to assess invasion, migration, proliferation, and apoptosis. DNA damage was evaluated via comet assay, immunofluorescence staining of γH2AX/53BP1 foci, and Western blot. In vivo effects on tumour progression and survival were examined in mouse models using immunohistochemistry and TUNEL apoptosis assays. Safety was also systematically evaluated. The combination of Tazemetostat and irradiation significantly suppressed PCa cell invasion, migration, and proliferation, and promoted apoptosis compared to radiation alone. In vivo, the combination group showed inhibited tumour growth, reduced invasion, induced apoptosis, and extended survival. Mechanistically, EZH2 inhibition enhanced radiation-induced DNA damage, increased double-strand breaks (DSBs), and impaired DSB repair capacity. The combination therapy exhibited a favourable safety profile without observable systemic toxicity. Tazemetostat effectively enhances radiosensitivity in PCa models by augmenting DNA damage and compromising repair mechanisms. These results support the clinical translation of EZH2 inhibition as a novel radiosensitising strategy for PCa patients.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-6 Promotes Pathological Angiogenesis in Oral Submucous Fibrosis by Suppressing USP10–VEGFR1 Interaction","authors":"Chunyu Li,&nbsp;Lingshuang Han,&nbsp;Zhenhao Wang,&nbsp;Yihang Xie,&nbsp;Xiaoping Xu,&nbsp;Qianming Chen,&nbsp;Liang Xie","doi":"10.1111/jcmm.71324","DOIUrl":"https://doi.org/10.1111/jcmm.71324","url":null,"abstract":"<p>Oral submucous fibrosis (OSF) is a chronic, progressive, premalignant disorder with expanding epidemiology, rising annual incidence, and increasing malignant transformation rates. Therefore, elucidating its pathogenesis and establishing early intervention strategies remain urgent priorities. In this study, we evaluated the interplay between USP10 and IL-6 and its potential influence on the development of oral submucous fibrosis. Immunohistochemistry and immunofluorescence were used to examine the correlation among IL-6, USP10, and pathological angiogenesis in OSF clinical samples and mouse models, revealing high IL-6 expression in the inflammatory microvasculature alongside downregulated USP10. Functional experiments on human umbilical vein endothelial cells (HUVECs) in vitro, including administration of recombinant human IL-6, demonstrated that USP10 inhibited angiogenesis, cell migration, and cell proliferation, and that targeting USP10 reversed IL-6-mediated pathological angiogenesis. RNA sequencing further identified differentially expressed genes in HUVECs, while mass spectrometry, western blotting, and co-immunoprecipitation uncovered that USP10 interacts with vascular endothelial growth factor receptor 1 (VEGFR1) and inhibits its ubiquitination, thereby suppressing angiogenesis. Collectively, these findings indicate that IL-6 promotes pathological angiogenesis by suppressing USP10 and its interaction with VEGFR1, thus accelerating OSF progression, and suggest that targeting USP10 may represent a promising mechanism for further investigation in OSF therapy.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-23 Receptor and Interleukin-17 Receptor A: Splice Variants, Isoforms and Their Relationship With Periodontitis—A Systematic Review and Bioinformatic Analysis","authors":"Mario Alberto Alarcón-Sánchez,&nbsp;Celia Guerrero-Velázquez,&nbsp;Daniel Ortuño-Sahagún,&nbsp;Sarah Monserrat Lomelí-Martínez,&nbsp;Julieta Sarai Becerra-Ruiz,&nbsp;Javier Flores-Fraile,&nbsp;Artak Heboyan","doi":"10.1111/jcmm.71325","DOIUrl":"https://doi.org/10.1111/jcmm.71325","url":null,"abstract":"<p>This systematic review aimed to: (1) identify the splicing variants of <i>IL23R</i> and <i>IL17RA</i> reported in the literature; (2) perform a multiple alignment analysis to describe the isoforms of IL-23R and IL-17RA; and (3) compare the expression levels of IL-23R, IL-17RA, and their soluble isoforms (sIL-23R and sIL-17RA) in patients with periodontitis and periodontally healthy individuals. The study protocol followed PRISMA guidelines and was registered in PROSPERO (CRD420251267367). Six databases (PubMed, ScienceDirect, Scopus, Web of Science, EBSCO, and Google Scholar) were searched without restrictions on year or language. The descriptors used were: ‘Interleukin-23 Receptor,’ ‘IL-23R,’ ‘Interleukin-17 Receptor A’ ‘IL-17RA,’ ‘Alternative Splicing,’ ‘Splice Variants,’ ‘Isoforms,’ and ‘Periodontitis.’ The bioinformatics analysis was performed using CLUSTALW (V.1.83), InterPro and DeepTMHMM. Risk of bias was assessed with the QUIN and JBI tools for cross-sectional studies. Of 104 articles, four in vitro studies and eight cross-sectional studies were included. Qualitative analysis revealed that to date there are 32 splicing variants of the <i>IL23R</i> gene, while only one splicing variant has been reported for <i>IL17RA</i>. CLUSTALW, InterPro and DeepTMHMM analysis showed that these splicing variants result in 23 isoforms which can be soluble forms, complete intracellular peptides, truncated extracellular or intracellular peptides, or complete structures with truncated extracellular and/or intracellular domains. All studies had a low risk of bias. IL-23R and IL-17RA exhibit structural diversity resulting from alternative splicing, with IL-23R demonstrating significantly greater isoform complexity. However, the biological significance of these isoforms in periodontitis remains unclear and requires further investigation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanistic Study of Melatonin Regulation of p16Ink4a and Oct4 in Anti-Cellular Senescence","authors":"Yang Xu,&nbsp;Cong Zhang,&nbsp;Li Wang,&nbsp;Xiaoyu Chen","doi":"10.1111/jcmm.71321","DOIUrl":"https://doi.org/10.1111/jcmm.71321","url":null,"abstract":"<p>Melatonin is a multifunctional indole hormone with established roles in anti-aging and tissue regeneration. Although it has been shown to modulate key senescence-associated markers such as p16Ink4a (p16) and OCT4, the underlying molecular mechanisms remain incompletely understood. MC3T3-E1 cells were treated with melatonin to evaluate its effects on p16 and OCT4 expression using Western blot and RT-qPCR. Isothermal titration calorimetry (ITC) and molecular docking were employed to investigate protein–protein interactions and structural binding patterns. VDR knockdown experiments were performed to assess functional causality. In addition, osteogenic differentiation was evaluated in bone marrow-derived mesenchymal stem cells (BMSCs) using alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. Melatonin significantly downregulated p16 and upregulated OCT4 expression without affecting cell viability. ITC analysis revealed that melatonin does not directly bind to p16 or OCT4, but both proteins interact with the vitamin D receptor (VDR) with moderate affinity. Molecular docking further supported stable binding conformations between VDR and p16/OCT4. Functionally, VDR knockdown disrupted the balance of p16 and OCT4 expression and impaired osteogenic differentiation, as evidenced by decreased ALP activity and reduced mineralized nodule formation. These findings identify VDR as a critical mediator of melatonin signalling and reveal a novel VDR-centered regulatory axis linking senescence and stemness pathways. This mechanism provides new insights into the anti-senescence and pro-regenerative effects of melatonin and suggests potential therapeutic strategies for aging-related diseases such as osteoporosis.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxoplasma gondii-Derived Soluble Factors Induce G2/M Phase Accumulation and p53-Associated Mitochondrial Apoptosis in Human Umbilical Cord Mesenchymal Stem Cells","authors":"Wei Zhou,&nbsp;Tingyu Chen,&nbsp;Ziping Yang,&nbsp;Jinjing Huang,&nbsp;Xinyi Lai,&nbsp;Jie Liu,&nbsp;Jiaqi Chu,&nbsp;Juanhua Quan","doi":"10.1111/jcmm.71312","DOIUrl":"10.1111/jcmm.71312","url":null,"abstract":"<p><i>Toxoplasma gondii</i> infection poses potential risks to stem cell-based therapeutic applications; however, the effects of parasite-derived soluble factors on mesenchymal stem cells remain unclear. Here, we investigated the impact of <i>T. gondii</i>-derived soluble factors (Tg-SFs) on human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). hUC-MSCs were exposed to Tg-SFs generated in a Transwell co-culture system, and cellular phenotypes and p53 signalling were analysed using integrated functional and molecular approaches. Tg-SFs induced upper-chamber multiplicity of infection (MOI)-dependent cytotoxicity in hUC-MSCs, accompanied by cytoskeletal remodelling and nuclear condensation. Tg-SFs exposure caused marked G2/M phase accumulation, which was accompanied by reduced expression of Cyclin A2, Cyclin B1, and Cyclin E2 and increased p21 expression. In addition, Tg-SFs exposure reduced phosphorylation of CDK1 at Thr161. Tg-SFs-exposed hUC-MSCs underwent significant apoptosis, as evidenced by PARP and Caspase-3 cleavage. Mechanistically, Tg-SFs promoted accumulation of total p53 protein and selective phosphorylation of p53 at Ser15 and Ser392, and modulated Bcl-2 family proteins by upregulating Bax, BID, Bak, Bad, and Puma while downregulating Bcl-xL and Mcl-1. Pharmacological inhibition of p53 with PFT-α and siRNA-mediated p53 knockdown partially reversed these effects, indicating that p53 signalling contributes substantially, but not exclusively, to Tg-SFs-induced mitochondrial apoptosis. These findings indicate that <i>T. gondii</i>-derived soluble factors impair hUC-MSC viability through G2/M phase accumulation and p53-associated mitochondrial apoptosis, highlighting a potential safety consideration for MSC-based applications under parasite-associated conditions.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148759854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to ‘Integration of Single-Cell and RNA-Seq Data to Explore the Role of Focal Adhesion-Related Genes in Osteoporosis’","authors":"","doi":"10.1111/jcmm.71291","DOIUrl":"https://doi.org/10.1111/jcmm.71291","url":null,"abstract":"<p>X. Shi, Q. Fu, J. Mao, et al., “Integration of Single-Cell and RNA-Seq Data to Explore the Role of Focal Adhesion-Related Genes in Osteoporosis,” <i>Journal of Cellular and Molecular Medicine</i> 28 (2024): e18271, https://doi.org/10.1111/jcmm.18271.</p><p>In Xiaojian Shi et al., the Western blot (WB) band of RNF24 in Figure 6D was presented incorrectly due to a technical error during image preparation by the authors. The corrected image is shown below. The authors confirm all results and conclusions of this article remain unchanged.</p><p>We apologize for this error.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Ultrastructural and Proteomic Analysis in DM1 Young Adults' Myoblasts: Stressed RER and Mitochondrial Dysfunction Involvement","authors":"Renata Del Carratore,&nbsp;Alessandra Falleni,&nbsp;Margherita Bernardeschi,&nbsp;Giada Frenzilli,&nbsp;Michela Ripolone,&nbsp;Sabrina Salani,&nbsp;Filippo Geraci,&nbsp;Fabiana Miraglia,&nbsp;Cristina Del Seppia","doi":"10.1111/jcmm.71289","DOIUrl":"https://doi.org/10.1111/jcmm.71289","url":null,"abstract":"<p>Myotonic dystrophy type 1 (DM1) is a progressive muscular disorder caused by the expansion of CTG repeats in the 3′ UTR of the DMPK gene. Although the pathogenic mechanisms remain unclear, recent evidence suggests that activation of innate immune responses may contribute to disease progression. In this study, we examined the ultrastructure and proteomic data of myoblasts from young adult DM1 patients carrying approximately 800 and 1300 CTG repeats in order to investigate a link between cellular stress and immune activation. We observed activation of the type I interferon (IFN-I) pathway associated with rough endoplasmic reticulum stress (sRER). The sRER response is likely triggered by the accumulation of toxic RNA species generated from the expanded DMPK allele. Our data suggest that this inappropriate activation of the IFN-I pathway contributes to muscle pathology, not by blocking differentiation directly, but through chronic stress signalling. These findings support a model in which innate immune dysregulation plays a central role in DM1 muscle degeneration and highlight the IFN1 pathway as a potential therapeutic target for restoring normal muscle function.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Significance of the Regulation Between tRF-31-U5YKFN8DYDZDD and BMPER in the Pathogenesis of Gastric Cancer (GC)","authors":"Yuejiao Huang,&nbsp;Xun Li,&nbsp;Yu Zhang,&nbsp;Xinliang Gu,&nbsp;Shiyi Qin,&nbsp;Ming Zheng,&nbsp;Han Wang,&nbsp;Shaoqing Ju","doi":"10.1111/jcmm.71320","DOIUrl":"https://doi.org/10.1111/jcmm.71320","url":null,"abstract":"<p>tsRNAs are a kind of small non-coding single-stranded RNA, which play an important role in many kinds of tumours. Previous studies have identified that tRF-31-U5YKFN8DYDZDD can be used as a novel tumour biomarker for the diagnosis and prognosis of gastric cancer (GC). In this study, we further explored the regulatory effect of tRF-31-U5YKFN8DYDZDD on tumour biological function in GC cells and related regulatory mechanisms. Inhibition of tRF-31-U5YKFN8DYDZDD can inhibit the proliferation, invasion, migration and angiogenesis of GC cells, while overexpression of tRF-31-U5YKFN8DYDZDD has the opposite effect. BMPER was shown to be a direct target of tRF-31-U5YKFN8DYDZDD in GC. Furthermore, the cytological effects of stable overexpression of BMPER were similar to the inhibition of tRF-31-U5YKFN8DYDZDD. And the attenuation of BMPER expression rescued the tRF-mediated promotion of GC cells. WB showed that up-regulation of tRF-31-U5YKFN8DYDZDD could increase the phosphorylation level of ERK and Smad1/5, and promote the expression of epithelial mesenchymal transition (EMT) and matrix metalloproteinases. Animal experiments in vivo show that down-regulation of tRF-31-U5YKFN8DYDZDD can effectively inhibit tumour growth. These data suggest that tRF-31-U5YKFN8DYDZDD is a new tumour-promoting factor and may be a potential new therapeutic target for GC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 16","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aerobic Endurance Training Modulates Cardiac Renin-Angiotensin System Peptides and Matrix Metalloproteinase Activity During Chronic Stress","authors":"Vinicius Guzzoni,&nbsp;Fabiana Gomes Ferreira,&nbsp;Lívia Bruni de Souza,&nbsp;Rebecca Salomão,&nbsp;Nicholas Kesler,&nbsp;Rodrigo Yokota,&nbsp;Nilsa Regina Damaceno-Rodrigues,&nbsp;Elia Garcia Caldini,&nbsp;Fernanda Klein Marcondes,&nbsp;Rita de Cássia Marqueti,&nbsp;Steven T. Haller,&nbsp;David J. Kennedy,&nbsp;Lauren G. Koch,&nbsp;Dulce Elena Casarini,&nbsp;Tatiana Sousa Cunha","doi":"10.1111/jcmm.71218","DOIUrl":"10.1111/jcmm.71218","url":null,"abstract":"<p>To investigate the involvement of metalloproteinases (MMPs) in the context of endurance training and their interactions with renin-angiotensin signalling (RAS) in stress-induced pathophysiological responses. Trained rats were submitted to 8-weeks of endurance treadmill training with chronic mild stress (CMS), TS rats, and without CMS (T). Non-trained rats (NTS and NT groups) were submitted to identical procedures except for training. NTS and TS groups were submitted to a CMS protocol for 3 weeks. Elevated corticosterone levels indicate an initial triggering factor that mediates the downstream intracellular signalling networks related to the MMPs and RAS activation after CMS. Endurance training confers cardioprotection against the stress response by lowering the Ang 3–7 levels, whereas increased activity of MMPs was observed in TS rats. Chronic stress disrupts the cardiac function, MMPs, and RAS activation by increasing the cardiac activity of the MMP-2 activity and Ang 1–9 levels with concomitant reduction of cardiac and blood levels of Ang 1–7. Stress also reduced circulating levels of Ang 1–9 and Ang 1–5, Ang 1–7 metabolites, along with increased Ang III (2–8). Aerobic endurance training is a potential exercise-based strategy that counteracts the stress-related disturbances in the MMPs and RAS signalling pathways.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"30 15","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.71218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}