[Insulin promotes BAMBI expression and inhibits inflammation in renal cortex of diabetic rats]
Dan Liang1, Can Peng1, Yawen Xiao1
1Department of Pathophysiology, Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang 550025, China.
Abstract:
Objective To explore the expression of renal cortex bone morphogenetic protein and activating protein membrane binding inhibitor (BAMBI), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck like protein containing a CARD-2 (ASC-2), caspase-1, inflammatory mediators and related fibrosis markers in renal cortex of diabetic mellitus (DM) rats treated with insulin. Methods SD rats were randomly divided into 3 groups: a normal control group, a DM group and an insulin treatment group. Each group included 8 rats. The DM rat model was established by streptozotocin (STZ). Four weeks after STZ injection, the rats in the insulin treatment group was subcutaneously injected with insulin at the dose of 8 U/kg once, three times each day for successive 6 weeks, and then sacrificed finally. The expression of BAMBI, NLRP3 and epithelial cadherin (E-cadherin) in the renal cortex were detected by immunohistochemistry. The expression of BAMBI, NLRP3, ASC-2, caspase-1, α-smooth muscle actin (α-SMA), fibronectin (FN) and type IV collagen (Col4) in the renal cortex were detected by Western blot analysis. The mRNA levels of BAMBI and NLRP3 in the renal cortex were measured by real-time quantitative PCR, and the levels of interleukin-1β (IL-1β) and IL-18 in the renal cortex were tested by ELISA. The correlation between BAMBI and NLRP3 was analyzed by Spearman method. Results Compared with the normal control group, the expression of NLRP3, ASC-2, caspase-1, α-SMA, FN and Col4 significantly increased, but BAMBI and E-cadherin significantly decreased in the renal cortex of DM group. However, the expression of NLRP3, ASC-2, caspase-1, α-SMA, FN, Col4, IL-1β and IL-18 in the insulin-treated group were lower than those in the DM group, but the expression of BAMBI and E-cadherin were higher. According to the correlation analysis, there was a negative correlation between the expression of BAMBI and NLRP3 in the DM group and insulin treatment group. Conclusion Insulin can restore the expression of BAMBI in the renal cortex of DM rats, and then inhibit the activation of NLRP3, thus reducing the renal inflammatory response in the kidney of DM rats and preventing or delaying the progression of diabetic nephropathy.
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