STEMIN and YAP5SA, the future of heart repair?

IF 2.8 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Experimental Biology and Medicine Pub Date : 2024-10-31 eCollection Date: 2024-01-01 DOI:10.3389/ebm.2024.10246

Nada Bejar, Siyu Xiao, Dinakar Iyer, Azeez Muili, Adeniyi Adeleye, Bradley K McConnell, Robert J Schwartz

{"title":"STEMIN and YAP5SA, the future of heart repair?","authors":"Nada Bejar, Siyu Xiao, Dinakar Iyer, Azeez Muili, Adeniyi Adeleye, Bradley K McConnell, Robert J Schwartz","doi":"10.3389/ebm.2024.10246","DOIUrl":null,"url":null,"abstract":"This review outlines some of the many approaches taken over a decade or more to repair damaged hearts. We showcase the recent breakthroughs in organ regeneration elicited by reprogramming factors OCT3/4, SOX2, KLF4, and C-MYC (OKSM). Transient OKSM transgene expression rejuvenated senescent organs in mice. OKSM transgenes also caused murine heart cell regeneration. A triplet alanine mutation of the N-terminus of Serum Response Factor's MADS box SRF153(A3), termed STEMIN, and the YAP mutant, YAP5SA synergized and activated OKSM and NANOG in adult rat cardiac myocytes; thus, causing rapid nuclear proliferation and blocked myocyte differentiation. In addition, ATAC seq showed induced expression of growth factor genes FGFs, BMPs, Notchs, IGFs, JAK, STATs and non-canonical Wnts. Injected STEMIN and YAP5SA synthetic modifying mRNA (mmRNA) into infarcted adult mouse hearts, brought damaged hearts back to near normal contractility without severe fibrosis. Thus, STEMIN and YAP5SA mmRNA may exert additional regenerative potential than OKSM alone for treating heart diseases.","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560420/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/ebm.2024.10246","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

This review outlines some of the many approaches taken over a decade or more to repair damaged hearts. We showcase the recent breakthroughs in organ regeneration elicited by reprogramming factors OCT3/4, SOX2, KLF4, and C-MYC (OKSM). Transient OKSM transgene expression rejuvenated senescent organs in mice. OKSM transgenes also caused murine heart cell regeneration. A triplet alanine mutation of the N-terminus of Serum Response Factor's MADS box SRF153(A3), termed STEMIN, and the YAP mutant, YAP5SA synergized and activated OKSM and NANOG in adult rat cardiac myocytes; thus, causing rapid nuclear proliferation and blocked myocyte differentiation. In addition, ATAC seq showed induced expression of growth factor genes FGFs, BMPs, Notchs, IGFs, JAK, STATs and non-canonical Wnts. Injected STEMIN and YAP5SA synthetic modifying mRNA (mmRNA) into infarcted adult mouse hearts, brought damaged hearts back to near normal contractility without severe fibrosis. Thus, STEMIN and YAP5SA mmRNA may exert additional regenerative potential than OKSM alone for treating heart diseases.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

STEMIN 和 YAP5SA，心脏修复的未来？

本综述概述了十多年来修复受损心脏的多种方法。我们展示了重编程因子OCT3/4、SOX2、KLF4和C-MYC（OKSM）最近在器官再生方面取得的突破。瞬时 OKSM 转基因表达使小鼠衰老的器官重新焕发活力。OKSM 转基因还能使小鼠心脏细胞再生。血清反应因子 MADS 框 SRF153(A3) N 端的三重丙氨酸突变（称为 STEMIN）和 YAP 突变体 YAP5SA 能协同激活成年大鼠心肌细胞中的 OKSM 和 NANOG，从而导致核快速增殖并阻止心肌细胞分化。此外，ATAC seq 显示诱导了生长因子基因 FGFs、BMPs、Notchs、IGFs、JAK、STATs 和非经典 Wnts 的表达。将 STEMIN 和 YAP5SA 合成修饰 mRNA（mmRNA）注射到梗塞的成年小鼠心脏中，可使受损心脏恢复到接近正常的收缩能力，且不会出现严重的纤维化。因此，在治疗心脏疾病方面，STEMIN 和 YAP5SA mmRNA 可能比单独使用 OKSM 发挥更大的再生潜力。

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分钟内获得全文去求助

来源期刊

Experimental Biology and Medicine 医学-医学：研究与实验

CiteScore

6.00

自引率

0.00%

发文量

157

审稿时长

1 months

期刊介绍： Experimental Biology and Medicine (EBM) is a global, peer-reviewed journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. EBM provides both research and review articles as well as meeting symposia and brief communications. Articles in EBM represent cutting edge research at the overlapping junctions of the biological, physical and engineering sciences that impact upon the health and welfare of the world''s population. Topics covered in EBM include: Anatomy/Pathology; Biochemistry and Molecular Biology; Bioimaging; Biomedical Engineering; Bionanoscience; Cell and Developmental Biology; Endocrinology and Nutrition; Environmental Health/Biomarkers/Precision Medicine; Genomics, Proteomics, and Bioinformatics; Immunology/Microbiology/Virology; Mechanisms of Aging; Neuroscience; Pharmacology and Toxicology; Physiology; Stem Cell Biology; Structural Biology; Systems Biology and Microphysiological Systems; and Translational Research.

期刊最新文献

STEMIN and YAP5SA, the future of heart repair? Fructose metabolism is unregulated in cancers and placentae. Subunit-specific mechanisms of isoflurane-induced acute tonic inhibition in dentate gyrus granule neuron.