Zhenhua Li1, Lantao Liu1, Ning Hou1, Yao Song2, Xiangbo An2, Youyi Zhang2, Xiao Yang1, Jian Wang3. 1. State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, China. 2. Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China. 3. State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, Beijing 100071, China wangjian7773@126.com.
Abstract
AIMS: Overexpression of either member of the miR-199 family, miR-199a-5p, or miR-199b-5p (hereinafter referred to as miR-199a or miR-199b) promotes pathological cardiac hypertrophy, but little is known about the role of endogenous miR-199 in cardiac development and disease. Our study aimed to determine the physiological function of the endogenous miR-199 family in cardiac homeostasis maintenance. METHODS AND RESULTS: We generated a sponge transgenic mouse model with a specific disruption of miR-199 in the heart. To our surprise, we found that knockdown of endogenous miR-199 caused physiological cardiac hypertrophy characterized by an increased heart weight and cardiomyocyte size, but with normal cardiac morphology and function. Furthermore, we also identified PGC1α as the target gene of the miR-199 family, and PGC1α was also increased in sponge transgenic mice. CONCLUSION: Inhibition of endogenous miR-199 led to physiological cardiac hypertrophy probably due to the up-regulation of PGC1α, uncovering a surprising role for endogenous miR-199 in the maintenance of cardiac homeostasis. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Overexpression of either member of the miR-199 family, miR-199a-5p, or miR-199b-5p (hereinafter referred to as miR-199a or miR-199b) promotes pathological cardiac hypertrophy, but little is known about the role of endogenous miR-199 in cardiac development and disease. Our study aimed to determine the physiological function of the endogenous miR-199 family in cardiac homeostasis maintenance. METHODS AND RESULTS: We generated a sponge transgenicmouse model with a specific disruption of miR-199 in the heart. To our surprise, we found that knockdown of endogenous miR-199 caused physiological cardiac hypertrophy characterized by an increased heart weight and cardiomyocyte size, but with normal cardiac morphology and function. Furthermore, we also identified PGC1α as the target gene of the miR-199 family, and PGC1α was also increased in sponge transgenic mice. CONCLUSION: Inhibition of endogenous miR-199 led to physiological cardiac hypertrophy probably due to the up-regulation of PGC1α, uncovering a surprising role for endogenous miR-199 in the maintenance of cardiac homeostasis. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Carmen C Sucharov; David P Kao; J David Port; Anis Karimpour-Fard; Robert A Quaife; Wayne Minobe; Karin Nunley; Brian D Lowes; Edward M Gilbert; Michael R Bristow Journal: JCI Insight Date: 2017-01-26