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2015 ; 8
(3
): 2321-33
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Reduced beta 2 glycoprotein I improves diabetic nephropathy via inhibiting
TGF-?1-p38 MAPK pathway
#MMPMID26045739
Wang T
; Chen SS
; Chen R
; Yu DM
; Yu P
Int J Clin Exp Pathol
2015[]; 8
(3
): 2321-33
PMID26045739
show ga
PURPOSE: 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). METHODS: 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. RESULTS: ?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. CONCLUSIONS: ?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.