The Effects TGF-β/Smads Signaling Pathway Plays On Gli-1 Of Hedgehog Signaling Pathway In Experimental Renal Tissues Of Diabetic Nephropathy

Objective: To explore the expression of Gli-1 that is from Hedgehog signaling pathway, TGF-β1 and Smad3 proteins which are from TGF-β/Smads signal pathway in experimental diabetic nephropathy(diabetic nephropathy, DN) renal tissues and the correlation among the three ones. Methods: 60 male SD rats were injected low dose streptozotocin and fed with hish fat and sucro diets to establish diabetes nephropathy model.After success established the DN animal model, than the experimental rats were randomly divided into five groups, each group often rats, normal control group(group A), diabetic nephropathy model group(group B), treat with benazepril group(group C), treat with irbesartan group(group D), treat with benazepril and irbesartan group(group E). Then all rats were killed after 8 weeks. To detect the expression of Gli-1, TGF-β1 and Smad3 proteins and the correlation among the three proteins, paraffin embedding and immunohistochemistry technique are used in experimental animal renal tissues. Results: The immunohistochemical staining showed that in the diabetic nephropathy group(group B), benazepril group(group C), irbesartan group(group D), combined with benazepril and irbesartan group(group E), Gli-1, Smad3, TGF-β1 proteins in renal tissues were significantly higher than that of normal control group(group A)(P<0.05); benazepril group(group C), irbesartan group(group D), combined with benazepril and irbesartan group(group E). In renal tissues, Smad3, Gli-1 TGF-β1 expression level were lower than that of diabetic nephropathy group(group B)(P<0.05); Joint that combined with benazepril and irbesartan group(group E) expression under the benazepril group(group C) and irbesartan group(group D)(P<0.05); The benazepril group(group C) and irbesartan group(group D) expression are not obviously different(P>0.05). TGF-β1, Gli-1 Smad3 protein expression of normal control group(group A) in the rats renal tissues are not obviously different. After eight weeks, the TGF-β1, Gli-1, Smad3 protein expression in DN groups(group B, C, D, E) increased, significantly higher than the normal control group(group A). DN kidney tissues, TGF-β1, Gli-1 and Smad3 protein expression are significantly consistent, and they are positively related. Conclusion:(1) The increasing expression of Gli-1, TGF-β1 and Smad3 in experimental diabetic nephropathy rats renal tissues may increase the DN kidney damage through strengthening the Hedgehog signaling pathway and TGF beta/Smads signaling pathway activity.(2)The TGF beta/Smads signal pathway activates Hedgehog signaling pathways by activating Hedgehog Gli-1 protein in signaling pathways,and the two pathways work together to promote the DN disease progression.