BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathway
Abstract 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 in...
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| Format: | Article |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-01936-5 |
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| author | Weili Liu Xinxing Wang Zhusong Mei Jingbo Gong lishuang Huang Xiujie Gao Yun Zhao Jing Ma Lingjia Qian |
| author_facet | Weili Liu Xinxing Wang Zhusong Mei Jingbo Gong lishuang Huang Xiujie Gao Yun Zhao Jing Ma Lingjia Qian |
| author_sort | Weili Liu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-18T04:04:49Z |
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| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:04:49Z |
| publishDate | 2017-05-01 |
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| series | Scientific Reports |
| spelling | doaj.art-ee9ef2f1c4a04b96a07597df2a250bdc2022-12-21T21:21:37ZengNature PortfolioScientific Reports2045-23222017-05-017111310.1038/s41598-017-01936-5BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathwayWeili Liu0Xinxing Wang1Zhusong Mei2Jingbo Gong3lishuang Huang4Xiujie Gao5Yun Zhao6Jing Ma7Lingjia Qian8Tianjin Institute of Health and Environmental MedicineTianjin Institute of Health and Environmental MedicineBeijing Institute of Basic Medical SciencesBeijing Institute of Basic Medical SciencesBeijing Institute of Basic Medical SciencesTianjin Institute of Health and Environmental MedicineBeijing Institute of Basic Medical SciencesBeijing Institute of Basic Medical SciencesBeijing Institute of Basic Medical SciencesAbstract 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.https://doi.org/10.1038/s41598-017-01936-5 |
| spellingShingle | Weili Liu Xinxing Wang Zhusong Mei Jingbo Gong lishuang Huang Xiujie Gao Yun Zhao Jing Ma Lingjia Qian BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathway Scientific Reports |
| title | BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathway |
| title_full | BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathway |
| title_fullStr | BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathway |
| title_full_unstemmed | BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathway |
| title_short | BNIP3L promotes cardiac fibrosis in cardiac fibroblasts through [Ca2+]i-TGF-β-Smad2/3 pathway |
| title_sort | bnip3l promotes cardiac fibrosis in cardiac fibroblasts through ca2 i tgf β smad2 3 pathway |
| url | https://doi.org/10.1038/s41598-017-01936-5 |
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