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.
ASJC Scopus subject areas
- Management, Monitoring, Policy and Law
- Health, Toxicology and Mutagenesis
Chang, R. L., Nithiyanantham, S., Kuo, W. W., Pai, P. Y., Chang, T. T., Lai, C. H., Chen, R. J., Vijaya Padma, V., Huang, C. Y., & Huang, C. Y. (認可的出版社/出版中). Overexpression of IGF-IIRα regulates cardiac remodeling and aggravates high salt induced apoptosis and fibrosis in transgenic rats. Environmental Toxicology. https://doi.org/10.1002/tox.22676