TMEM182 inhibits myocardial differentiation of human iPS cells by maintaining the activated state of Wnt/β-catenin signaling through an increase in ILK expression

IF 2.5 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY FASEB bioAdvances Pub Date : 2024-10-14 DOI:10.1096/fba.2024-00086
Hirofumi Morihara, Shunichi Yokoe, Shigeo Wakabayashi, Shinji Takai
{"title":"TMEM182 inhibits myocardial differentiation of human iPS cells by maintaining the activated state of Wnt/β-catenin signaling through an increase in ILK expression","authors":"Hirofumi Morihara,&nbsp;Shunichi Yokoe,&nbsp;Shigeo Wakabayashi,&nbsp;Shinji Takai","doi":"10.1096/fba.2024-00086","DOIUrl":null,"url":null,"abstract":"<p>Transmembrane protein 182 (TMEM182) is notably abundant in muscle and adipose tissue, but its role in the heart remains unknown. This study examined the contribution of TMEM182 in the differentiation of human induced pluripotent stem cells (hiPSCs) into cardiomyocytes. For this, we generated hiPSCs overexpressing TMEM182 in a doxycycline-inducible manner and induced their differentiation into cardiomyocytes. On Day 12 of differentiation, expression of the cardiomyocyte markers, <i>TNNT2</i> and <i>MYH6</i>, was significantly decreased in TMEM182-overexpressing cells. Additionally, we found that phosphorylation of GSK-3β (Ser9) and β-catenin (Ser552) was increased during TMEM182 overexpression, suggesting activation of Wnt/β-catenin signaling. We further focused on integrin-linked kinase (ILK) as the mechanism by which TMEM182 activates Wnt/β-catenin signaling. Evaluation showed that ILK expression was increased in cells overexpressing TMEM182. These results suggest that TMEM182 maintains Wnt/β-catenin signaling in an activated state after mesoderm formation by increasing ILK expression, thereby suppressing hiPSCs differentiation into cardiomyocytes.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00086","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FASEB bioAdvances","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1096/fba.2024-00086","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Transmembrane protein 182 (TMEM182) is notably abundant in muscle and adipose tissue, but its role in the heart remains unknown. This study examined the contribution of TMEM182 in the differentiation of human induced pluripotent stem cells (hiPSCs) into cardiomyocytes. For this, we generated hiPSCs overexpressing TMEM182 in a doxycycline-inducible manner and induced their differentiation into cardiomyocytes. On Day 12 of differentiation, expression of the cardiomyocyte markers, TNNT2 and MYH6, was significantly decreased in TMEM182-overexpressing cells. Additionally, we found that phosphorylation of GSK-3β (Ser9) and β-catenin (Ser552) was increased during TMEM182 overexpression, suggesting activation of Wnt/β-catenin signaling. We further focused on integrin-linked kinase (ILK) as the mechanism by which TMEM182 activates Wnt/β-catenin signaling. Evaluation showed that ILK expression was increased in cells overexpressing TMEM182. These results suggest that TMEM182 maintains Wnt/β-catenin signaling in an activated state after mesoderm formation by increasing ILK expression, thereby suppressing hiPSCs differentiation into cardiomyocytes.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
TMEM182 通过增加 ILK 的表达维持 Wnt/β-catenin 信号的激活状态,从而抑制人 iPS 细胞的心肌分化
跨膜蛋白182(TMEM182)在肌肉和脂肪组织中含量显著丰富,但其在心脏中的作用仍不清楚。本研究考察了TMEM182在人类诱导多能干细胞(hiPSCs)向心肌细胞分化过程中的作用。为此,我们以多西环素诱导的方式生成了过表达 TMEM182 的 hiPSCs,并诱导其分化为心肌细胞。在分化的第 12 天,TMEM182-过表达细胞中心肌细胞标志物 TNNT2 和 MYH6 的表达明显下降。此外,我们发现在过表达 TMEM182 的过程中,GSK-3β(Ser9)和β-catenin(Ser552)的磷酸化增加,这表明 Wnt/β-catenin 信号被激活。我们进一步研究了整合素连接激酶(ILK)作为TMEM182激活Wnt/β-catenin信号的机制。评估显示,在过表达 TMEM182 的细胞中,ILK 的表达增加。这些结果表明,TMEM182通过增加ILK的表达,使Wnt/β-catenin信号在中胚层形成后保持激活状态,从而抑制了hiPSCs向心肌细胞的分化。
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
FASEB bioAdvances
FASEB bioAdvances Multiple-
CiteScore
5.40
自引率
3.70%
发文量
56
审稿时长
10 weeks
期刊最新文献
Issue Information Medium-chain fatty acid receptor GPR84 deficiency leads to metabolic homeostasis dysfunction in mice fed high-fat diet TMEM182 inhibits myocardial differentiation of human iPS cells by maintaining the activated state of Wnt/β-catenin signaling through an increase in ILK expression Everything, everywhere, and all at once: A blueprint for supra-organization of core facilities New role of calcium-binding fluorescent dye alizarin complexone in detecting permeability from articular cartilage to subchondral bone
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1