Effect and mechanism of FoxO1 overexpression in rats with diabetic nephropathy
10.3760/cma.j.issn.1000-6699.2015.02.014
- VernacularTitle:FoxO1过表达对大鼠糖尿病肾病的影响及机制研究
- Author:
Yingni ZHOU
;
Qingzhu WANG
;
Guijun QIN
;
Feng GUO
;
Yuanyuan ZHANG
;
Lina WU
- Publication Type:Journal Article
- Keywords:
Forkhead transcription factor O1;
Diabetic mellitus,experimental;
Glomerular mesangial cells;
Cell proliferation
- From:
Chinese Journal of Endocrinology and Metabolism
2015;(2):155-161
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the role and molecular mechanism of forkhead transcription factor O1 (FoxO1) on proliferation of mesangial cells( MCs) in diabetic rats. Methods Empty lentiviral vector( LV-pSC-GFP) and the constitutively active FoxO1 lentiviral vector(LV-CA-FoxO1) were constructed. Diabetic rat model was established and rats were divided into diabetes group(DM group), diabetes with LV-pSC-GFP group(NC group), and diabetes with LV-CA-FoxO1 group(CA group). The normal SD rats of the same age were considered as the normal control group(NG group). The lentiviral vector was injected into the renal cortex of diabetic rats in corresponding groups. Body weight, blood glucose, 24 h urinary protein, urine albumin, serum creatinine, and blood urea nitrogen was detected at the end of 2 weeks, 4 weeks, and 8 weeks. The ratio of kidney weight/ body weight was counted and the renal cortex was reserved for light microscopy, electron microscopy and frozen section after rats were sacrificed in different groups. The mRNA level of FoxO1 and p27Kip1 were detected by real-time PCR. The protein expressions of FoxO1, p-FoxO1, and p27Kip1 were tested by Western blotting. Results The renal pathological changes were obviously ameliorated in CA group. Compared with DM group, the mRNA and protein expression of FoxO1 and p27Kip1 were significantly increased in CA group (P<0. 05), whereas there was no difference in the expression of p-FoxO1 protein(P > 0. 05). The p-FoxO1 / FoxO1 ratio was decreased ( P < 0. 05). All indexes had not reached statistical difference between NC group and DM group(P>0. 05). Conclusion Overexpression of FoxO1 in kidneys of diabetic rats can inhibit the proliferation of mesangial cells, and may through up-regulating the expression of p27Kip1 delay the progression of diabetic nephropathy.
