Yan Meiling, Mei Yu, Zhang Tianjun, Liu Zhou, Su Liyan, Xiao Yang, Zhong Xunlong, Lu Yanjie
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China; Guangdong Key Laboratory of Metabolic Disease Prevention and Treatment of Traditional Chinese Medicine, China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, China; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangzhou, China; Guangdong Key Laboratory of Metabolic Disease Prevention and Treatment of Traditional Chinese Medicine, China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
Int J Cardiol. 2024 Aug 1;408:132149. doi: 10.1016/j.ijcard.2024.132149. Epub 2024 May 7.
Ubiquitination is an enzymatic modification involving ubiquitin chains, that can be reversed by deubiquitination (DUB) enzymes. Ubiquitin-specific protease 7 (USP7), which is also known as herpes virus-associated ubiquitin-specific protease (HAUSP), has been shown to play a vital role in cardiovascular diseases. However, the underlying molecular mechanism by which USP7 regulates cardiomyocyte function has not been reported.
To understand the physiological function of USP7 in the heart, we constructed cardiomyocyte-specific USP7 conditional knockout mice.
We found that homozygous knockout mice died approximately three weeks after birth, while heterozygous knockout mice grew normally into adulthood. Severe cardiac dysfunction, hypertrophy, fibrosis, and cell apoptosis were observed in cardiomyocyte-specific USP7 knockout mice, and these effects were accompanied by disordered mitochondrial dynamics and cardiometabolic-related proteins.
In summary, we investigated changes in the growth status and cardiac function of cardiomyocyte-specific USP7 knockout mice, and preliminarily explored the underlying mechanism.
泛素化是一种涉及泛素链的酶促修饰，可被去泛素化（DUB）酶逆转。泛素特异性蛋白酶7（USP7），也被称为疱疹病毒相关泛素特异性蛋白酶（HAUSP），已被证明在心血管疾病中起重要作用。然而，USP7调节心肌细胞功能的潜在分子机制尚未见报道。
为了解USP7在心脏中的生理功能，我们构建了心肌细胞特异性USP7条件性敲除小鼠。
我们发现纯合敲除小鼠在出生后约三周死亡，而杂合敲除小鼠正常成长至成年。在心肌细胞特异性USP7敲除小鼠中观察到严重的心脏功能障碍、肥大、纤维化和细胞凋亡，这些影响伴随着线粒体动力学和心脏代谢相关蛋白的紊乱。
总之，我们研究了心肌细胞特异性USP7敲除小鼠的生长状态和心脏功能变化，并初步探讨了其潜在机制。
