title: Berberine ameliorates experimental diabetes-induced renal inflammation and fibronectin by inhibiting the activation of RhoA/ROCK signaling.
abstract: The accumulation of glomerular extracellular matrix proteins, especially fibronectin (FN), is a critical pathological characteristic of diabetic renal fibrosis. Inflammation mediated by nuclear factor-κB (NF-κB) plays a critical role in the pathogenesis of diabetic nephropathy (DN). RhoA/ROCK signaling is responsible for FN accumulation and NF-κB activation. Berberine (BBR) treatment significantly inhibited renal inflammation and thus improved renal damage in diabetes. Here, we study whether BBR inhibits FN accumulation and NF-κB activation by inhibiting RhoA/ROCK signaling and the underlying mechanisms involved. Results showed that BBR effectively inhibited RhoA/ROCK signaling activation in diabetic rat kidneys and high glucose-induced glomerular mesangial cells (GMCs) and simultaneously down-regulated NF-κB activity, which was accompanied by reduced intercellular adhesionmolecule-1, transforming growth factor-beta 1 and FN overproduction. Furthermore, we observed that BBR abrogated high glucose-mediated reactive oxygen species generation in GMCs. BBR and N-acetylcysteine inhibited RhoA/ROCK signaling activation in high glucose-exposed GMCs. Collectively, our data suggest that the renoprotective effect of BBR on DN partly depends on RhoA/ROCK inhibition. The anti-oxidative stress effect of BBR is responsible for RhoA/ROCK inhibition in DN.
authors.affiliation: Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Department of Pharmaceutical Engineering, Ocean College, Hainan University, Haikou 570228, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xie
authors.forename: Xiuting
authors.initials: X
authors.lastname: Chang
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shen
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009393:Nephritis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005353:Fibronectins; D016166:Free Radical Scavengers; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D001599:Berberine; D018799:Intercellular Adhesion Molecule-1; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D000111:Acetylcysteine
keywords: Berberine; DN; Diabetic nephropathy; ECM; Fibronectin; GMCs; ICAM-1; MDA; MYPT; N-acetylcysteine; NAC; NF-κB; ROCK; ROS; RhoA/ROCK; SOD; STZ; TGF-β1; diabetic nephropathy; extracellular matrix; glomerular mesangial cells; intercellular adhesionmolecule-1; malondialdehyde; myosin phosphatase; nuclear factor-kappa B; reactive oxygen species; rho kinase; streptozocin; superoxide dismutase; transforming growth factor-beta 1