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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/9921
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| Title: | Cardiac fibrosis in mouse expressing DsRed tetramers involves chronic autophagy and proteasome degradation insufficiency |
| Authors: | Chen, TH;Chen, MR;Chen, TY;Wu, TC;Liu, SW;Hsu, CH;Liou, GG;Kao, YY;Dong, GC;Chu, PH;Liao, JW;Lin, KM |
| Contributors: | Institute of Biomedical Engineering and Nanomedicine;Institute of Molecular and Genomic Medicine |
| 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 ofcardiac 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-kappaB 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. |
| Date: | 2016-08-02 |
| Relation: | Oncotarget. 2016 Aug 2;7(34):54274-54289. |
| Link to: | http://dx.doi.org/10.18632/oncotarget.11026 |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000385435000016 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84983568259 |
| Appears in Collections: | [林名釗] 期刊論文
[董國忠] 期刊論文
[劉淦光(2006-2014)] 期刊論文
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| PUB27494843.pdf | | 9478Kb | Adobe PDF | 539 | View/Open |
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