Uric acid up-regulates renin-angiotensin system via TLR2 inflammatory signaling pathway in adipocytes
10.3760/cma.j.issn.1000-6699.2018.08.011
- VernacularTitle:尿酸通过TLR2炎症信号通路上调脂肪细胞肾素-血管紧张素表达
- Author:
Junxia ZHANG
1
;
Bo DIAO
;
Zilin YUAN
;
Xue LIN
;
Jinxiu XU
Author Information
1. 中国人民解放军武汉总医院内分泌科
- Keywords:
Uric acid;
Toll-like receptor 2;
Inflammation;
Adipocyte;
Renin-angiotensin system
- From:
Chinese Journal of Endocrinology and Metabolism
2018;34(8):684-689
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the underlying mechanisms through which uric acid upregulates local renin-angiotensin system in adipocytes. Methods The primary cultured rat adipocytes were administered with 0, 1, 5, 10, and 15 mg/dl uric acid for 0, 12, 24, 48, and 72 h. Some of the pre-adipocytes were infected with siRNA-TLR2 or its negative control before differentiation. Then infected mature adipocytes were treated with 10 mg/dl uric acid for 48 h. After that procedure, mRNA levels of TLR2, TNF-α, IL-6, MCP-1, AGT, ACE1, AT1R, and AT2R were detected with real-time PCR method. The protein levels of TLR2 and NF-κB were detected by Western blotting. The concentrations of angiotensinⅡ( Ang Ⅱ) in the conditioned medium or cell lysate were measured using ELISA method. Results The mRNA levels mRNA of TLR2 increased in parallel with uric acid concentration. Moreover, it also increased with the time. By contrast, TLR2 mRNA expression decreased at 72 h. Uric acid increased levels of TNF-α, IL-6, and MCP-1 in adipocytes. It was also found that uric acid upregulated RAS components, including AGT, ACE1, AT1R, AT2R, and AngⅡ. However, siRNA-TLR2 infection significantly reduced the levels of TLR2 and NF-κB. As a result, both inflammatory cytokines and RAS components were significantly decreased in adipocytes. Conclusion Uric acid up-regulates RAS expression partially via TLR2 inflammatory signaling pathway in adipocytes.
