PMID: 25774384Mar 17, 2015Paper

CREG1 ameliorates myocardial fibrosis associated with autophagy activation and Rab7 expression

Biochimica Et Biophysica Acta
Cheng-hui YanYa-ling Han

Abstract

In cardiomyocytes subjected to stress, autophagy activation is a critical survival mechanism that preserves cellular energy status while degrading damaged proteins and organelles. However, little is known about the mechanisms that govern this autophagic response. Cellular repressor of E1A genes (CREG1) is an evolutionarily conserved lysosomal protein, and an important new factor in regulating tissues homeostasis that has been shown to antagonize injury of tissues or cells. In the present study, we aimed to investigate the regulatory role of CREG1 in cardiac autophagy, and to clarify autophagy activation mechanisms. First, we generated a CREG1 haploinsufficiency (Creg1(+/-)) mouse model, and identified that CREG1 deficiency aggravates myocardial fibrosis in response to aging or angiotensin II (Ang II). Conversely, exogenous infusion of recombinant CREG1 protein complete reversed cardiac damage. CERG1 deficiency in Creg1(+/-) mouse heart showed a market accumulation of autophagosome that acquired LC3II and beclin-1, and a decrease in autophagic flux clearance as indicated by upregulating the level of p62. Inversely, restoration of CREG1 activates cardiac autophagy, Furthermore, chloroquine, an inhibitor of lysosomal acidification...Continue Reading

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Citations

Apr 10, 2016·International Journal of Biological Macromolecules·Hui TaoKai-Hu Shi
Sep 14, 2016·Journal of Molecular Endocrinology·Lichun ZhouXiuzhen Han
Feb 26, 2016·Biology of Reproduction·Yanzhou YangYanrong Wang
Mar 21, 2017·Clinical and Experimental Pharmacology & Physiology·Lu LuBing Hui Wang
Jul 28, 2018·European Journal of Oral Sciences·Bo W NilsenKaren K Sørensen
Feb 27, 2019·Journal of Cellular Physiology·Mehrdad AghaeiVahid Khori
Jul 3, 2019·British Journal of Pharmacology·Chong-Chao HsiehPo-Len Liu
Nov 13, 2018·Frontiers in Cell and Developmental Biology·Gaby GhobrialLeonard Y Lee
Apr 23, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xingru YangBin Liu

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