School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China.
School of Mathematics and Statistics, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China.
Mol Med Rep. 2024 May;29(5). doi: 10.3892/mmr.2024.13193. Epub 2024 Mar 8.
Cardiac hypertrophy is one of the key processes in the development of heart failure. Notably, small GTPases and GTPase‑activating proteins (GAPs) serve essential roles in cardiac hypertrophy. RhoGAP interacting with CIP4 homologs protein 1 (RICH1) is a RhoGAP that can regulate Cdc42/Rac1 and F‑actin dynamics. RICH1 is involved in cell proliferation and adhesion; however, to the best of our knowledge, its role in cardiac hypertrophy remains unknown. In the present study, the role of RICH1 in cardiomyocyte hypertrophy was assessed. Cell viability was analyzed using the Cell Counting Kit‑8 assay and cells surface area (CSA) was determined by cell fluorescence staining. Reverse transcription‑quantitative PCR and western blotting were used to assess the mRNA expression levels of hypertrophic marker genes, such as Nppa, Nppb and Myh7, and the protein expression levels of RICH1, respectively. RICH1 was shown to be downregulated in isoproterenol (ISO)‑ or angiotensin II (Ang II)‑treated H9c2 cells. Notably, overexpression of RICH1 attenuated the upregulation of hypertrophy‑related markers, such as Nppa, Nppb and Myh7, and the enlargement of CSA induced by ISO and Ang II. By contrast, the knockdown of RICH1 exacerbated these effects. These findings suggested that RICH1 may be a novel suppressor of ISO‑ or Ang II‑induced cardiomyocyte hypertrophy. The results of the present study will be beneficial to further studies assessing the role of RICH1 and its downstream molecules in inhibiting cardiac hypertrophy.
心肌肥厚是心力衰竭发展过程中的关键过程之一。值得注意的是，小分子 GTP 酶和 GTP 酶激活蛋白（GAP）在心肌肥厚中发挥重要作用。与 CIP4 同源物蛋白 1（RICH1）相互作用的 RhoGAP 是一种可以调节 Cdc42/Rac1 和 F-肌动蛋白动态的 RhoGAP。RICH1 参与细胞增殖和黏附；然而，据我们所知，其在心肌肥厚中的作用尚不清楚。在本研究中，评估了 RICH1 在心肌细胞肥大中的作用。通过 Cell Counting Kit-8 检测分析细胞活力，通过细胞荧光染色测定细胞表面积（CSA）。逆转录-定量 PCR 和蛋白质印迹法分别用于评估肥厚标志物基因（如 Nppa、Nppb 和 Myh7）的 mRNA 表达水平和 RICH1 蛋白表达水平。结果显示，在异丙肾上腺素（ISO）或血管紧张素 II（Ang II）处理的 H9c2 细胞中，RICH1 表达下调。值得注意的是，过表达 RICH1 可减弱 ISO 和 Ang II 诱导的肥大相关标志物（如 Nppa、Nppb 和 Myh7）的上调和 CSA 的增大。相比之下，沉默 RICH1 则加剧了这些效应。这些发现表明 RICH1 可能是 ISO 或 Ang II 诱导的心肌细胞肥大的新型抑制因子。本研究的结果将有助于进一步研究评估 RICH1 及其下游分子在抑制心肌肥厚中的作用。
