Cardiac fibrosis, featuring abnormally elevated extracellular matrix accumulation, decreases tissue compliance, impairs cardiac function and accelerates heart failure. Mounting evidence suggests that the ubiquitin proteasome pathway is involved in cardiac fibrosis. In the present study, ubiquitin‐specific protease 2 (USP2) was identified as a novel therapeutic target in cardiac fibrosis. Indeed, USP2 expression was increased in angiotensin II–induced primary cardiac fibroblasts (CFs) from neonatal rats. In addition, USP2 inhibition suppressed CFs proliferation, collagen synthesis and cell cycle progression. Furthermore, USP2 interacted with β‐catenin, thereby regulating its deubiquitination and stabilization in CFs. To sum up, these findings revealed that USP2 has a therapeutic potential for the treatment of cardiac fibrosis.

中文翻译：

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泛素特异性蛋白酶 2 通过上调细胞周期蛋白 D1 和稳定 β-catenin 体外调节 Ang Ⅱ 诱导的心脏成纤维细胞活化


心脏纤维化的特点是细胞外基质积累异常升高，降低组织顺应性，损害心脏功能并加速心力衰竭。越来越多的证据表明，泛素蛋白酶体途径与心脏纤维化有关。在本研究中，泛素特异性蛋白酶 2 (USP2) 被确定为心脏纤维化的新治疗靶点。事实上，血管紧张素 II 诱导的新生大鼠原代心脏成纤维细胞 (CF) 中 USP2 表达增加。此外，USP2 抑制可抑制 CF 增殖、胶原蛋白合成和细胞周期进程。此外，USP2 与 β-catenin 相互作用，从而调节其去泛素化和 CF 中的稳定性。综上所述，这些发现表明 USP2 具有治疗心脏纤维化的潜力。