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|Title: ||Overexpression of IGF-IIRα regulates cardiac remodeling and aggravates high salt induced apoptosis and fibrosis in transgenic rats|
|Authors: ||Cha, Ruey-Lin;Chang, Ruey-Lin;Srinivasan, N;Nithiyanantham, Srinivasan;Kuo, Wei-Wen;Kuo, Wei-Wen;Pai, Pei-Ying;Pai, Pei-Ying;Chan, Tung-Ti;Chang, Tung-Ti;La, Chao-Hung;Lai, Chao-Hung;Che, Ray-Jade;Chen, Ray-Jade;Viswanadha, Viswanadha V;Padma, Viswanadha Vijaya;Hu, Chih-Yang;Huang, Chih-Yang;黃志揚;Huang;Chih-Yang|
|Issue Date: ||2019-09-18 10:57:55 (UTC+8)|
|Abstract: ||IGF-IIR activation regulates cardiac remodeling leading to apoptosis. Here, we identified the novel IGF-IIRα (150 KDa), a truncated IGF-IIR transcript enhances cardiac apoptosis under high-salt uptake in transgenic rat model. Echocardiographic analysis revealed decline in ejection fraction and fractional shortening percentage in IGF-IIRα (TG) rats. We found that IGF-IIRα TG rats developed severe apoptosis and fibrosis as identified through TUNEL assay and Masson's trichrome staining. Importantly, the heart functioning, apoptosis, and fibrosis were significantly affected under high-salt conditions in IGF-IIRα (TG) rats. Significant upregulation of apoptosis was evident from decreased Bcl-2, p-AKT, and p-PI3K expressions with concomitant increase in Bad, cytochrome C, cleaved caspase 3 levels. We found that, IGF-IIRα highly induced tissue fibrosis through collagen accumulation (col I, col III) and up regulated various fibrotic markers such as tPA, uPA, TGF-β, and vimentin expressions. The observed upregulation of fibrosis were significantly regulated under high-salt conditions and their over regulation under IGF-IIRα over expressions shows the key role of IGF-IIRα in promoting high-salt induced fibrosis. During IGF-IIRα over expression induced cardiotoxicity, under high salt condition, and it destroys the interaction between CHIP and HSF1, which promotes the degradation of HSF1 and results in upregulation of IGF-IIR/IGF-IIRα expressions. Altogether, the study unveils novel IGF-IIRα in the regulation of cardiac apoptosis and fibrosis under high-salt diet.|
|Relation: ||ENVIRONMENTAL TOXICOLOGY|
|Appears in Collections:||[生物科技學系] 期刊論文|
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