Rho-family GTPase 1 (Rnd1) is a biomechanical stress-sensitive activator of cardiomyocyte hypertrophy

Journal of Molecular and Cellular Cardiology
Annika KlugeDerk Frank

Abstract

Cardiac remodeling is induced by mechanical or humoral stress causing pathological changes to the heart. Here, we aimed at identifying the role of differentially regulated genes upon dynamic mechanical stretch. Microarray of dynamic stretch induced neonatal rat ventricular cardiomyocytes (NRVCMs) discovered Rho family GTPase 1 (Rnd1) as one of the significantly upregulated genes, a cardiac role of which is not known yet. Rnd1 was consistently upregulated in NRVCMs after dynamic stretch or phenylephrine (PE) stimulation, and in a mouse model of pressure overload. Overexpression of Rnd1 in NRVCMs activated the fetal gene program (including nppa and nppb) effected into a significant increase in cell surface area in untreated, stretched or PE-treated cells. Furthermore, Rnd1 overexpression showed a positive effect on cell proliferation as detected by significant increase in Ki67, Phosphohistone H3, and EdU positive NRVCMs. Through a Yeast two-hybrid screen and immunoprecipitation analysis, we identified Myozap, an intercalated disc protein, as novel interaction partner of Rnd1. Importantly, functional analysis of this interaction revealed the importance of RND1 in the RhoA and Myozap protein network that activates serum-response fa...Continue Reading

Citations

Nov 21, 2020·International Journal of Molecular Sciences·Jing ZhaoMasanori Yoshizumi
Nov 5, 2020·Cells·Ankush BorlepawarAshraf Yusuf Rangrez
Feb 9, 2021·Frontiers in Cell and Developmental Biology·Hongyu LiaoYifei Li
Apr 29, 2021·Journal of Biomedical Science·Lucia Sophie KilianAshraf Yusuf Rangrez
Oct 16, 2020·Small GTPases·Sara BasbousViolaine Moreau

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