Role of glucogen synthase kinase-3β in a rat kidney model of chronic allograft nephropathy
10.3760/cma.j.issn.0254-1785.2011.11.011
- VernacularTitle:磷酸化糖原合成酶激酶-3β在大鼠移植肾早期病理改变中的作用
- Author:
Yuxin WANG
;
Yiqin ZHANG
;
Huaifu LI
;
Jing YE
;
Hequn ZOU
;
Yanling SHI
;
Ling CHEN
;
Wenying ZHOU
- Publication Type:Journal Article
- Keywords:
Rats;
Kidney transplantation;
Chronic allograft nephropathy;
Glycogen synthasekinase 3
- From:
Chinese Journal of Organ Transplantation
2011;32(11):683-687
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression and significance of glucogen synthase kinase-3β (GSK-3β) in the pathogenesis of chronic allograft nephropathy (CAN) in rats.Methods Kidneys of Fisher (F344) rats as donors were orthotopically transplanted into Lewis (LEW) rats as recipients.The renal function and histopathological changes were observed at 4,8,12,16,and 24week post-transplantation.Phosphorylated GSK-3β (p-GSK-3β) protein and mRNA expression was determined by using immunohistological assays and RT-PCR respectively.Results Our data showed that 24-h urinary protein excretion in CAN rats was increased significantly at week 16 as compared with F344/LEW controls.Allografts showed markedly increased mononuclear cells infiltration and presented with severe interstitial fibrosis and tubular atrophy at 16 and 24 week post-transplantation.p-GSK-3β expression (protein/mRNA) was down-regulated in rat kidneys with CAN,and the decrease became more significant over time after transplantation.p-GSK-3β expression was correlated significantly with 24-h urinary protein excretion,serum creatinine levels,tubulointerstitial mononuclear cells infiltration,smooth muscle cells migration in vascular wall,and interstitial fibrosis.Conclusion It was concluded that GSK-3β down-regulation was the key event that may be involved in mononuclear cells infiltration and vascular SMCs migration at early stage,and interstitial fibrosis and allograft nephroangiosclerosis at later stage of CAN pathogenesis in rats.
