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Function of TGF‐β Regulated NcRNAs in Cardiac Hypertrophy
Author(s) -
Yang Xiao
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.470.5
Subject(s) - autophagy , muscle hypertrophy , cardiac function curve , genetically modified mouse , transgene , microbiology and biotechnology , downregulation and upregulation , biology , endogeny , pi3k/akt/mtor pathway , transforming growth factor , pressure overload , medicine , signal transduction , endocrinology , cardiac hypertrophy , heart failure , apoptosis , biochemistry , gene
Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to physiological or pathological stimuli. The role of TGF‐b signaling in cardiac hypertrophy has been being debated. We have previously shown that the function of endogenous TGF‐b/Smad signaling in maintaining cardiac homeostasis involves the downregulation of miRNAs inducing cardiac hypertrophy. We found that miR‐199a acts as a key regulator of cardiac autophagy and cardiac hypertrophy. We generated cardiac‐specific miR‐199a transgenic mice and demonstrated that overexpression of miR‐199a was sufficient to inhibit cardiomyocyte autophagy and induced cardiac hypertrophy in vivo. Mechanistically, miR‐199a impaired cardiomyocyte autophagy in a cell‐autonomous manner by targeting glycogen synthase kinase 3β (GSK3β)/mammalian target of rapamycin (mTOR) complex signaling. Activation of autophagy using rapamycin was sufficient to restore cardiac autophagy and decrease cardiac hypertrophy in miR‐199a transgenic mice. Interestingly, inhibition of endogenous miR‐199 led to physiological cardiac hypertrophy, uncovering a surprising role for endogenous miR‐199 in the maintenance of cardiac hemostasis. Very recently, we found that a TGF‐b regulated lncRNA induced cardiac hypertrophy in transgenic mice. These results suggest that targeting ncRNAs regulated by TGF‐b is a potential therapeutic strategy for cardiac disease.