| Autor: |
Weili, Liu, Xinxing, Wang, Zhusong, Mei, Jingbo, Gong, Lishuang, Huang, Xiujie, Gao, Yun, Zhao, Jing, Ma, Lingjia, Qian |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Scientific Reports |
| ISSN: |
2045-2322 |
| Popis: |
Fibrosis is an important, structurally damaging event that occurs in pathological cardiac remodeling, leading to cardiac dysfunction. BNIP3L is up-regulated in pressure overload-induced heart failure and has been reported to play an important role in cardiomyocyte apoptosis; however, its involvement in cardiac fibroblasts (CFs) remains unknown. We prove for the first time that the expression of BNIP3L is significantly increased in the CFs of rats undergoing pressure overload-induced heart failure. Furthermore, this increased BNIP3L expression was confirmed in cultured neonatal rat CFs undergoing proliferation and extracellular matrix (ECM) protein over-expression that was induced by norepinephrine (NE). The overexpression or suppression of BNIP3L promoted or inhibited NE-induced proliferation and ECM expression in CFs, respectively. In addition, [Ca2+]i, transforming growth factor beta (TGF-β) and the nuclear accumulation of Smad2/3 were successively increased when BNIP3L was overexpressed and reduced when BNIP3L was inhibited. Furthermore, the down-regulation of TGF-β by TGF-β-siRNA attenuated the increase of BNIP3L-induced fibronectin expression. We also demonstrated that the increase of BNIP3L in CFs was regulated by NE-AR-PKC pathway in vitro and in vivo. These results reveal that BNIP3L is a novel mediator of pressure overload-induced cardiac fibrosis through the [Ca2+]i-TGF-β-Smad2/3 pathway in CFs. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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