Fibroblast-Specific Depletion of Human Antigen R Alleviates Myocardial Fibrosis Induced by Cardiac Stress

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2024-06-01 DOI:10.1016/j.jacbts.2024.03.004

Mallikarjun Patil PhD , Sarojini Singh PhD , Praveen Kumar Dubey PhD , Sultan Tousif PhD , Prachi Umbarkar PhD , Qinkun Zhang MD , Hind Lal PhD , Mary Kathryn Sewell-Loftin PhD , Channakeshava Sokke Umeshappa PhD , Yohannes T. Ghebre PhD , Steven Pogwizd MD , Jianyi Zhang MD, PhD , Prasanna Krishnamurthy PhD

{"title":"Fibroblast-Specific Depletion of Human Antigen R Alleviates Myocardial Fibrosis Induced by Cardiac Stress","authors":"Mallikarjun Patil PhD , Sarojini Singh PhD , Praveen Kumar Dubey PhD , Sultan Tousif PhD , Prachi Umbarkar PhD , Qinkun Zhang MD , Hind Lal PhD , Mary Kathryn Sewell-Loftin PhD , Channakeshava Sokke Umeshappa PhD , Yohannes T. Ghebre PhD , Steven Pogwizd MD , Jianyi Zhang MD, PhD , Prasanna Krishnamurthy PhD","doi":"10.1016/j.jacbts.2024.03.004","DOIUrl":null,"url":null,"abstract":"<div><p>Cardiac fibrosis can be mitigated by limiting fibroblast-to-myofibroblast differentiation and proliferation. Human antigen R (HuR) modulates messenger RNA stability and expression of multiple genes. However, the direct role of cardiac myofibroblast HuR is unknown. Myofibroblast-specific deletion of HuR limited cardiac fibrosis and preserved cardiac functions in pressure overload injury. Knockdown of HuR in transforming growth factor-β1–treated cardiac fibroblasts suppressed myofibroblast differentiation and proliferation. HuR deletion abrogated the expression and messenger RNA stability of cyclins D1 and A2, suggesting a potential mechanism by which HuR promotes myofibroblast proliferation. Overall, these data suggest that inhibition of HuR could be a potential therapeutic approach to limit cardiac fibrosis.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 6","pages":"Pages 754-770"},"PeriodicalIF":8.4000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001001/pdfft?md5=1dfef1dc400593b49b939db150e6f189&pid=1-s2.0-S2452302X24001001-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC: Basic to Translational Science","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452302X24001001","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Cardiac fibrosis can be mitigated by limiting fibroblast-to-myofibroblast differentiation and proliferation. Human antigen R (HuR) modulates messenger RNA stability and expression of multiple genes. However, the direct role of cardiac myofibroblast HuR is unknown. Myofibroblast-specific deletion of HuR limited cardiac fibrosis and preserved cardiac functions in pressure overload injury. Knockdown of HuR in transforming growth factor-β1–treated cardiac fibroblasts suppressed myofibroblast differentiation and proliferation. HuR deletion abrogated the expression and messenger RNA stability of cyclins D1 and A2, suggesting a potential mechanism by which HuR promotes myofibroblast proliferation. Overall, these data suggest that inhibition of HuR could be a potential therapeutic approach to limit cardiac fibrosis.

查看原文本刊更多论文

纤维母细胞特异性清除人类抗原 R 可缓解心脏应激诱发的心肌纤维化

通过限制成纤维细胞向肌成纤维细胞的分化和增殖，可减轻心脏纤维化。人类抗原 R（HuR）可调节信使 RNA 的稳定性和多种基因的表达。然而，心肌成纤维细胞 HuR 的直接作用尚不清楚。心肌成纤维细胞特异性删除 HuR 限制了心脏纤维化，并保护了压力过载损伤时的心脏功能。在转化生长因子-β1处理的心肌成纤维细胞中敲除HuR抑制了心肌成纤维细胞的分化和增殖。删除 HuR 可抑制细胞周期蛋白 D1 和 A2 的表达和信使 RNA 的稳定性，这表明 HuR 有可能促进心肌成纤维细胞增殖。总之，这些数据表明，抑制HuR可能是限制心脏纤维化的一种潜在治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.