Both ERK/MAPK and TGF-Beta/Smad signaling pathways play a role in the kidney fibrosis of diabetic mice accelerated by blood glucose fluctuation.
BACKGROUND
The notion that diabetic nephropathy is the leading cause of renal fibrosis prompted us to investigate the effects of blood glucose fluctuation (BGF) under high glucose condition on kidney in the mice.


METHODS
The diabetic and BGF animal models were established in this study. Immunohistochemistry, Western blot, and RT-PCR analysis were applied to detect the expression of type I collagen, matrix metalloproteinase-1 (MMP1), metalloproteinase inhibitor 1 (TIMP1), transforming growth factor beta 1 (TGF- β 1), phosphorylated-ERK, p38, smad2/3, and Akt.


RESULTS
BGF treatment increased type I collagen synthesis by two times compared with the control. The expression of MMP1 was reduced markedly while TIMP1 synthesis was enhanced after BGF treatment. ERK phosphorylation exhibits a significant increase in the mice treated with BGF. Furthermore, BGF can markedly upregulate TGF- β 1 expression. The p-smad2 showed 2-fold increases compared with the only diabetic mice. However, p-AKT levels were unchanged after BGF treatment.


CONCLUSIONS
These data demonstrate that BGF can accelerate the trend of kidney fibrosis in diabetic mice by increasing collagen production and inhibiting collagen degradation. Both ERK/MAPK and TGF- β /smad signaling pathways seem to play a role in the development of kidney fibrosis accelerated by blood glucose fluctuation.
Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Xiaoyun
X
Cheng
Wenke
W
Gao
Yongyan
Y
Dang
Xia
X
Liu
Yujuan
Y
Li
Xu
X
Peng
Xiyun
X
Ye
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001786:Blood Glucose; D024042:Collagen Type I; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D020781:Matrix Metalloproteinase 1