Activation of RhoA/ROCK regulates NF-kappa B signaling pathway in experimental diabetic nephropathy

作者：Xie, Xi; Peng, Jing; Chang, Xiuting; Huang, Kaipeng; Huang, Juan; Wang, Shaogui; Shen, Xiaoyan; Liu, Peiqing; Huang, Heqing^*

来源：Molecular and Cellular Endocrinology, 2013, 369(1-2): 86-97.

DOI：10.1016/j.mce.2013.01.007

• Diabetic nephropathy
• RhoA/ROCK
• NF-kappa B
• Fibronectin
• Fasudil

Both RhoA/ROCK and NF-kappa B signaling pathways play important roles in the pathogenesis of diabetic nephropathy (DN). However, it remains unknown whether and how RhoA/ROCK regulates NF-kappa B signaling in diabetic kidneys. In cultured glomerular mesangial cells (GMCs), the high glucose-activated NF-kappa B 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-kappa B pathway. Furthermore, NF-kappa B-regulated inflammatory factors ICAM-1 and TGF-beta 1 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-kappa B nuclear translocation, and significantly reduced the renal FN, ICAM-1 and TGF-beta 1 protein levels. Thus, the RhoA/ROCK pathway may regulate NF-kappa B to upregulate inflammatory genes and mediate the development of DN.

• 出版日期2013-4-30
• 单位海南大学; 中山大学