Cardiac fibrosis in mouse expressing DsRed tetramers involves chronic autophagy and proteasome degradation insufficiency

doi:10.18632/oncotarget.11026

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Periodical Articles > Item 310902800/31037

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/31037

Title:	Cardiac fibrosis in mouse expressing DsRed tetramers involves chronic autophagy and proteasome degradation insufficiency
Authors:	Chen, Tsung-Hsien Chen, Mei-Ru Chen, Tzu-Yin Wu, Tzu-Chin Liu, Shan-Wen Hsu, Ching-Han Liou, Gan-Guang Kao, Yu-Ying Dong, Guo-Chung Chu, Pao-Hsien Liao, Jiunn-Wang Lin, Kurt Ming-Chao
Contributors:	Natl Hlth Res Inst, Inst Biomed Engn & Nanomed Natl Tsing Hua Univ, Inst Biomed Engn & Environm Sci Natl Hlth Res Inst, Inst Mol & Genom Med Chia Nan Univ Pharm & Sci, Dept Biotechnol Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Cardiol Natl Chung Hsing Univ, Grad Inst Vet Pathobiol
Keywords:	protein aggregation cardiac hypertrophy fibrosis heart failure proteasome Pathology Section system
Date:	2016-08
Issue Date:	2018-01-18 11:40:20 (UTC+8)
Publisher:	Impact Journals Llc
Abstract:	Proteinopathy in the heart which often manifests excessive misfolded/aggregated proteins in cardiac myocytes can result in severe fibrosis and heart failure. Here we developed a mouse model, which transgenically express tetrameric DsRed, a red fluorescent protein (RFP), in an attempt to mimic the pathological mechanisms of cardiac fibrosis. Whilst DsRed is expressed and forms aggregation in most mouse organs, certain pathological defects are specifically recapitulated in cardiac muscle cells including mitochondria damages, aggresome-like residual bodies, excessive ubiquitinated proteins, and the induction of autophagy. The proteinopathy and cellular injuries caused by DsRed aggregates may be due to impaired or overburdened ubiquitin-proteasome system and autophagy-lysosome systems. We further identified that DsRed can be ubiquitinated and associated with MuRF1, a muscle-specific E3 ligase. Concomitantly, an activation of NF-kappa B signaling and a strong TIMP1 induction were noted, suggesting that RFP-induced fibrosis was augmented by a skewed balance between TIMP1 and MMPs. Taken together, our study highlights the molecular consequences of uncontrolled protein aggregation leading to congestive heart failure, and provides novel insights into fibrosis formation that can be exploited for improved therapy.
Relation:	Oncotarget, v.7 n.34, pp.54274-54289
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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