Erythropoietin suppresses the expressions of TGF-β1 and collagen in rat cardiac fibroblasts induced by angiotensin Ⅱ
10.3321/j.issn:0253-3758.2008.07.014
- VernacularTitle:促红细胞生成素抑制血管紧张素Ⅱ诱导的大鼠心脏成纤维细胞中转化生长因子β1和胶原的表达
- Author:
Xin-Jin ZHANG
1
;
Ye-Xin MA
;
Yuan WEN
;
Xue-Jing XU
Author Information
1. 云南省第二人民医院
- Keywords:
Endomyocardial fibrosis;
Erythropoietin;
Angiotensin Ⅱ;
Fibroblasts;
Transforming growth factor beta 1;
Collagen
- From:
Chinese Journal of Cardiology
2008;36(7):636-640
- CountryChina
- Language:Chinese
-
Abstract:
Objective Recent studies have shown cardiac protection effects of erythropoietin (EPO).The present experiment was designed to investigate the effects of EPO on TGF-β1, nitric oxide synthase ( NOS), collagen contents induced by angiotensin Ⅱ ( Ang Ⅱ ) in rat cardiac fibroblasts (CFs) and explore the roles of PI3-K/Akt signaling pathway on related effects.Methods Neonatal rat CFs was isolated by collgenase and trypsinase digestion methods.PBS, EPO, Ang Ⅱ in the absence or presence of LY294002, an inhibitor of PI3-K, or L-NAME, an inhibitor of NOS, were added to CFs and cultured for 24 hours.The concentration of collagen Ⅰ and collagen Ⅲ in culture medium were quantitated by ELISA.The levels of nitric oxide (NO) and the activities of NOS as well as NOS isofonns were measured by chemical enzymic method.Western blot was applied to detecting the protein expressions of Akt, p-Akt, eNOS, iNOS, and TGF-β1.Results The concentrations of collagen Ⅰ and collagen Ⅲ in CFs culture medium were significantly increased while the level of NO was significantly decreased by Ang Ⅱ and these changes were significantly suppressed by EPO in a dose dependent manner.The effects of EPO on eNOS and NO could be blocked by LY294002.L-NAME could block EPO's effect on NO but not on the eNOS expression.The suppression effects on expressions of TGF-β1 and collagen by Ang Ⅱ in CFs were blocked by both LY294002 and L-NAME.conclusion EPO suppresses the upregulated expressions of TGF-β1 and increased production of collagen induced by Ang Ⅱ through activating the PI3-K/Akt signaling pathway in neonatal rat CFs.
