Renoprotective action by erythropoietin via BMP/SMAD signaling pathway in renal anemia in rats and its mechanism
10.7652/jdyxb201506010
- VernacularTitle:促红细胞生成素通过 BMP/SMAD 通路对肾性贫血大鼠肾脏的保护作用及其机制
- Author:
Yan ZHANG
;
Yinlan LI
;
Menghua CHEN
- Publication Type:Journal Article
- Keywords:
renal anemia;
erythropoietin;
BMP/SMAD;
hepcidin;
BMP-6
- From:
Journal of Xi'an Jiaotong University(Medical Sciences)
2015;(6):765-769,800
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of erythropoietin (EPO)on the kidney of renal anemia rats and further explore the renoprotective action and possible mechanisms.Methods A total of 90 SD rats were randomly divided into 5 groups:normal control rats (NC),simple anemia group (SA),iron + EPO group (IR+EPO),erythropoietin group (EPO),and iron group (IR)with 18 in each.The rats were sacrificed after 4 weeks’ treatment with intragastrically-injected adenine.Serum creatinine (Scr),blood urea nitrogen (Bun),hemoglobin (Hb),hematocrit (Hct),and hepcidin were measured with automated hematology analyzer.The expressions of bone morphogenetic protein-6 (BMP-6 ),a serine/threonine kinase receptor-1 (SMAD-1 )and serine/threonine kinase receptor-4 (SMAD-4)in the kidney were detected by immunohistochemistry and Western blot.Results ①The results of general indicators:BUN and Scr in IR + EPO group and EPO group were lower than those in SA group (P <0.01).Hb and Hct in IR + EPO group and EPO group were increased significantly compared with those in SA group (P <0.01).Hepcidin was significantly increased in simple anemia group (P <0.01).② ELISA results showed that Hepcidin was lower in IR + EPO group and EPO group than in SA group (P <0.01).③ The results of pathological observation indicated that EPO could reduce rat renal pathology and function.④ Immunohistochemistry revealed that SMAD-4,SMAD-1 and BMP-6 were expressed in the rat glomerular cells and renal tubular epithelial cells.⑤ Western blot further indicated that the expression of SMAD-4 was significantly decreased in IR + EPO group and EPO group (P < 0.01 ).The expression of SMAD-1 in IR+EPO group and EPO group was decreased (P <0.05)while that of BMP-6 was elevated in IR+EPO group and EPO group (P <0.01 ).Conclusion The expression and secretion of hepcidin were inhibited by EPO via the BMP/SMAD pathway,which further corrects anemia and exerts a renal protective effect.
