1. Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy
- Author
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Xie, Xi, Peng, Jing, Chang, Xiuting, Huang, Kaipeng, Huang, Juan, Wang, Shaogui, Shen, Xiaoyan, Liu, Peiqing, and Huang, Heqing
- Subjects
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NF-kappa B , *CELLULAR signal transduction , *DIABETIC nephropathies , *CELL culture , *CHROMOSOMAL translocation , *EXTRACELLULAR matrix , *HEMAGGLUTININ - Abstract
Abstract: Both RhoA/ROCK and NF-κB signaling pathways play important roles in the pathogenesis of diabetic nephropathy (DN). However, it remains unknown whether and how RhoA/ROCK regulates NF-κB signaling in diabetic kidneys. In cultured glomerular mesangial cells (GMCs), the high glucose-activated NF-κB nuclear translocation and DNA binding activity were attenuated by ROCK inhibitor Y27632 or dominant-negative RhoA mutant, indicating that RhoA/ROCK signaling regulates high glucose-activated NF-κB pathway. Furthermore, NF-κB-regulated inflammatory factors ICAM-1 and TGF-β1 were markedly increased in high glucose-treated GMCs, leading to accumulation of fibronectin (FN), an important component of extracellular matrix (ECM), This effect was also effectively attenuated by Y27632 or dominant-negative RhoA mutant. In STZ-induced diabetic rats, treatment with ROCK inhibitor fasudil suppressed the RhoA/ROCK activation and NF-κB nuclear translocation, and significantly reduced the renal FN, ICAM-1 and TGF-β1 protein levels. Thus, the RhoA/ROCK pathway may regulate NF-κB to upregulate inflammatory genes and mediate the development of DN. [Copyright &y& Elsevier]
- Published
- 2013
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