Protective effects of C/EBPα on podocytes in diabetic nephropathy
10.3760/cma.j.issn.1001-7097.2018.05.006
- VernacularTitle:C/EBPα对糖尿病肾病足细胞保护作用的研究
- Author:
Fangfang ZHOU
1
;
Liwen ZHANG
;
Jian LIU
;
Ji YING
;
Yunzi LIU
;
Fang ZHONG
;
Weiming WANG
;
Nan CHEN
Author Information
1. 200025,上海交通大学医学院肾脏病研究所上海交通大学医学院附属瑞金医院肾脏科
- Keywords:
Diabetic nephropathy;
Podocytes;
Mouse,gene knockout;
C/EBPα
- From:
Chinese Journal of Nephrology
2018;34(5):355-360
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of C/EBPα knockout in podocyte on diabetic nephropathy and its mechanisms.Methods C/EBPαloxp/loxp mice were crossed with podocin-cre mice to obtain F1 hybrids and then propagated until homozygous mice (C/EBPαf/f) were obtained.Diabetic nephropathy (DN) models were established by low-dose streptozotocin (STZ,100 mg/kg) administration after 25 weeks of normal diet or 45％ high-fat diet treatment,and biochemical indicators of blood and urea were measured.The morphological characteristics and the proteins regulating oxidative stress and mitochondrial function were detected.Results The type 2 DN models were successfully constructed based on transgenic mice.The kidneys of 8-month-old C/EBPαf/f mice did not show obvious morphological changes,but after constructing DN models,they showed obvious renal impairment,inflammation and oxidative stress.Compared with wild-type DN mice,the protein levels of nephrin and E-cadherin in DN C/EBPαf/f mice with DN were significantly decreased (P ＜ 0.01);fibronectin and Nrf2 protein levels were all increased (all P ＜ 0.05).Keap1,phospho-AMPK and mitochondrial function related genes Pgc-1α protein levels were all decreased (all P ＜ 0.05).Conclusion Podocyte C/EBPα knockout exacerbates diabetic nephropathy by promoting fibrosis and inhibiting Pgc-1α-mediated mitochondrial antioxidant function.
