KLF15 protects against isoproterenol-induced cardiac hypertrophy via regulation of cell death and inhibition of Akt/mTOR signaling
作者
Gao, L;Guo, YD;Liu, XF;Shang, DY;Du, YJ
作者单位
[Gao, Li; Shang, Deya] Shandong Univ, Prov Hosp, Jinan, Peoples R China.;-;[Guo, Yudong; Liu, Xiaofeng; Du, Yongjian] Fifth Peoples Hosp Jinan, Dept Neurol, Jinan, Peoples R China.
摘要
Increasing evidence indicate that the Kruppel-like factor KLF15, a member of Cys2/His2 zinc-finger DNA-binding proteins, attenuates cardiac hypertrophy. However, the role of KLF15 in cardiovascular system is largely unknown and the exact molecular mechanism of its protective function is not fully elucidated. In the present study, we established a mouse model of cardiac hypertrophy and found that KLF15 expression was down-regulated in hypertrophic hearts. To evaluate the roles of KLF15 in cardiac hypertrophy, we generated transgenic mice overexpressing KLF15 of KLF15 knockdown mice and subsequently induced cardiac hypertrophy. The results indicated that KLF15 overexpression protects mice from ISO-induced cardiac hypertrophy, with reduced ratios of heart weight (HW)/body weight (BW) and cross-sectional area. We also observed that KLF15 overexpression attenuated cardiac fibrosis, inhibited apoptosis and induced autophagy in cardiomyocytes compared with KLF15 knockdown mice. More importantly, we found that the KLF15 overexpression inhibited the Akt/mTOR signaling pathway. Taken together, our findings imply that KLF15 possesses potential anti-hypertrophic and anti-fibrotic functions, possibly via regulation of cell death pathways and the inhibition of Akt/mTOR axis. KLF15 may constitute an efficient candidate drug for the treatment of heart failure and other cardiovascular diseases. (C) 2017 Elsevier Inc. All rights reserved.
关键词
TRANSCRIPTION FACTOR KLF5; KRUPPEL-LIKE FACTORS; ANGIOTENSIN-II; EXPRESSION; ACTIVATION; DIFFERENTIATION; KLF5/BTEB2; FIBROSIS
基本信息
