Smaller thioredoxin-like proteins sharing SH3 domains. Although its expression is confined towards the cardiac and skeletal muscle, the physiological role of SH3BGR within the heart is poorly understood. Interestingly, we observed a considerable upregulation of SH3BGR in failing hearts of mice and human patients with hypertrophic cardiomyopathy. Along these lines, the overexpression of SH3BGR exhibited a substantial raise inside the expression of hypertrophic markers (Nppa and Nppb) and improved cell surface location in neonatal rat ventricular cardiomyocytes (NRVCMs), whereas its knockdown attenuated cellular hypertrophy. Mechanistically, utilizing serum Gavestinel sodium salt Purity response element (SRF) response element-driven luciferase assays inside the presence or the absence of RhoA or its inhibitor, we identified that the pro-hypertrophic effects of SH3BGR are mediated by means of the RhoA RF axis. Moreover, SH3BGR knockdown resulted in the induction of apoptosis and lowered cell viability in NRVCMs by means of apoptotic Hippo AP signaling. Taking these outcomes collectively, we right here show that SH3BGR is vital for keeping cytoskeletal integrity and cellular viability in NRVCMs by means of its modulation with the SRF/YAP signaling pathways. Search phrases: SH3BGR; cardiac hypertrophy; SRF signaling; Hippo signaling; apoptosisPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.1. Introduction Trisomy 21, the presence of a supernumerary chromosome 21, final results in among probably the most frequent chromosomal abnormalities in humans