title: Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy.
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.
authors: Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors: Xi
authors: X
authors: Xie
authors: Jing
authors: J
authors: Peng
authors: Xiuting
authors: X
authors: Chang
authors: Kaipeng
authors: K
authors: Huang
authors: Juan
authors: J
authors: Huang
authors: Shaogui
authors: S
authors: Wang
authors: Xiaoyan
authors: X
authors: Shen
authors: Peiqing
authors: P
authors: Liu
authors: Heqing
authors: H
authors: Huang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D005947:Glucose