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https://ir.cnu.edu.tw/handle/310902800/31037
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| 標題: | Cardiac fibrosis in mouse expressing DsRed tetramers involves chronic autophagy and proteasome degradation insufficiency |
| 作者: | 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 |
| 貢獻者: | 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 |
| 關鍵字: | protein aggregation
cardiac hypertrophy
fibrosis
heart failure
proteasome
Pathology Section
system |
| 日期: | 2016-08 |
| 上傳時間: | 2018-01-18 11:40:20 (UTC+8) |
| 出版者: | Impact Journals Llc |
| 摘要: | 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. |
| 關聯: | Oncotarget, v.7 n.34, pp.54274-54289 |
| 顯示於類別: | [生物科技系(所)] 期刊論文
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