Reduced beta 2 glycoprotein I improves diabetic nephropathy via inhibiting TGF-?1-p38 MAPK pathway.

ABSTRACT: Beta 2 glycoprotein I (?2GPI) has been shown the positive effect on diabetic atherosclerosis and retinal neovascularization. ?2GPI can be reduced by thioredoxin-1, resulting in the reduced state of ?2GPI. The possible protective effects of ?2GPI and reduced ?2GPI on diabetic nephropathy (DN) are not fully elucidated. The purpose of this study was to test a hypothesis that ?2GPI and reduced ?2GPI would improve DN in streptozotocin (STZ) induced diabetic mice and high-glucose (HG) exposed rat mesangial cell (RMC).The STZ-induced Balb/c mice and HG exposed RMCs were administrated with ?2-GPI and reduced ?2-GPI at different time and concentrations gradient respectively. The changes of glomerular structure and expression of collagen IV, TGF-?1, p38 MAPK and phospho-p38 MAPK in renal cortical and mesangial cells were observed by immunohistochemical techniques, quantitative real-time PCR and western blot with or without the treatment of ?2-GPI and reduced ?2-GPI.?2GPI and reduced ?2GPI improved early clinical and pathological changes of DN in STZ-diabetic mice. Treatment with ?2GPI and reduced ?2GPI in the STZ-diabetic mice and HG exposed RMCs resulted in decrease expression levels of TGF-?1 and collagen IV, with concomitant decrease in phospho-p38 MAPK expression.?2GPI and reduced ?2GPI improved renal structural damage and kidney function. The renoprotective and antifibrosis effects of ?2GPI and reduced ?2GPI on DN were closely associated with suppressing the activation of the TGF-?1-p38 MAPK pathway.

SUBMITTER: Wang T 

PROVIDER: S-EPMC4440048 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature