Interlukin-22 induces transforming growth factor -β1 high expression and the correlation with diabetic renal fibrosis
10.3760/cma.j.issn.1000-6699.2017.09.013
- VernacularTitle:白细胞介素22介导转化生长因子-β1高表达与糖尿病肾纤维化相关性分析
- Author:
Yi LIU
1
;
Linshuang ZHAO
;
Yanyan LIN
;
Jinling XU
Author Information
1. 广州军区武汉总医院内分泌科
- Keywords:
Interlukin-22;
Transforming growth factor-β1;
Diabetic nephropathy;
Fibrosis
- From:
Chinese Journal of Endocrinology and Metabolism
2017;33(9):769-775
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of interlukin-22 (IL-22) on diabetic renal fibrosis and its possible mechanisms. Methods C57 BL/ 6 mice were randomized to normal control group ( NC group), diabetic nephropathy control group ( DN group), recombinant interlukin-22 ( rIL-22) group, and interlukin-22 antibody (Anti-IL-22) group. 8 weeks after successful establishment of diabetes model, mice were injected intraperitoneally with 200 ng/ g rIL-22, Anti-IL-22 or equal 0. 1% bovine serum albumin (BSA) twice a week for 4 weeks. After the intervention, blood glucose, kidney function and 24 h urine microalbumin creatinine ratio were measured. Renal pathological changes and collagen deposition were observed under the light microscope, and semiquantitative assessment of renal sclerosis and fibrosis were evaluated at the same time. The mRNA expression of transforming growth factor ( TGF)-β1 was determined by realtime PCR. The protein expressions of α-smooth muscle actin (α-SMA), E-cadherin, and fibronetin (FN) were examined by Western blotting. The protein expressions of collagenⅢ were examined by immunohistochemical analysis. Results After 4 weeks of intervention, the 24 h urine microalbumin creatinine ratio decreased significantly in the Anti-IL-22 group ( P<0. 05). Renal tubular epithelial cells vacuolar degeneration, protein cast formation, and glomerular mesangial expansion were observed under the light microscope. And the lesions were more severe in the rIL-22 group, whereas improved in the Anti-IL-22 group. Meanwhile, the collagen deposition was in accordance with the tubular injury score. Moreover, TGF-β1 gene expression increased significantly in the rIL-22 group (P<0. 01). α-SMA and E-cadherin, epithelial-mesenchymal transition (EMT) markers, increased or decreased significantly in the rIL-22 group respectively (P<0. 05). FN and collagen Ⅲ, extracellular matrix ( ECM ) proteins, increased significantly in the rIL-22 group as well ( P <0. 05). Conclusions IL-22 may induce renal tubular epithelial cells TGF-β1 high expression. As a consequence, this contributes to EMT occurance and ECM accumulation, eventually accelerating the progression of diabetic renal fibrosis.
