Reduced beta 2 glycoprotein I improves diabetic nephropathy via inhibiting TGF-β1-p38 MAPK pathway.

PURPOSE Beta 2 glycoprotein I (β2GPI) has been shown the positive effect on diabetic atherosclerosis and retinal neovascularization. β2GPI can be reduced by thioredoxin-1, resulting in the reduced state of β2GPI. The possible protective effects of β2GPI and reduced β2GPI on diabetic nephropathy (DN) are not fully elucidated. The purpose of this study was to test a hypothesis that β2GPI and reduced β2GPI would improve DN in streptozotocin (STZ) induced diabetic mice and high-glucose (HG) exposed rat mesangial cell (RMC). METHODS The STZ-induced Balb/c mice and HG exposed RMCs were administrated with β2-GPI and reduced β2-GPI at different time and concentrations gradient respectively. The changes of glomerular structure and expression of collagen IV, TGF-β1, 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 β2-GPI and reduced β2-GPI. RESULTS β2GPI and reduced β2GPI improved early clinical and pathological changes of DN in STZ-diabetic mice. Treatment with β2GPI and reduced β2GPI in the STZ-diabetic mice and HG exposed RMCs resulted in decrease expression levels of TGF-β1 and collagen IV, with concomitant decrease in phospho-p38 MAPK expression. CONCLUSIONS β2GPI and reduced β2GPI improved renal structural damage and kidney function. The renoprotective and antifibrosis effects of β2GPI and reduced β2GPI on DN were closely associated with suppressing the activation of the TGF-β1-p38 MAPK pathway.