Role of HMGN1 in epithelial-mesenchymal transition of kidney tubules in diabetic nephropathy mice

Abstract

Objective This study aimed to investigate the renal expression change of high mobility of nucleosome binding protein 1 (HMGN1) in epithelia-mesenchymal transition (EMT) process, and to study the effect of HMGN1 on renal fibrosis in the diabetic nephropathy mice model. Methods 20 C57BL/6 mice were randomly divided into control group, model group, benazepril group, and insulin group. After 8 weeks of drug intervention, blood, urine and kidney tissue samples were taken from mice. The routine physiological and biochemical indexes were detected. Renal structure and fibrosis were detected by HE and Sirius red staining, respectively. Immunohistochemistry and in situ hybridization were used to investigate the protein and mRNA expression levels of HMGN1, CD68, F4/80, α-smooth muscle actin (α-SMA), and E-cadherin in renal tissue. Results Blood glucose, renal index, and urinary albumin to creatinine ratio (UACR) were significantly higher in the model group than those in the normal group. In the model group, HE staining showed glomerular hypertrophy and interstitial inflammatory cell infiltration, and Sirius red showed collagen deposition in the renal tissue. Compared with normal group, HMGN1, CD68, F4/80 positive cell counts and α-SMA protein expression were all increased, while E-cadherin protein expression was downregulated in the model group (all P<0.05). The above indexes were not improved significantly in the benazepril group. And after intervention of insulin, the expression levels of CD68 positive cell count and α-SMA protein were decreased and the expression levels of E-cadherin protein were increased compared with the model group (all P<0.05). The correlation analysis showed that the level of HMGN1 was correlated with CD68, F4/80, α-SMA, E-cadherin and collagen protein, while CD68 and f4/80 were correlated with α-SMA, collagen protein and blood glucose, respectively (all P<0.05). Conclusion HMGN1 is involved in the progression of diabetic nephropathy fibrosis, and its underlying mechanism might be related to the macrophage-mediated EMT process. Key words: High-mobility group nucleosome-binding protein 1; Epithelial-mesenchymal transition; Diabetic nephropathies; Renal fibrosis