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: Xi Xie, Xiuting Chang, Lei Chen, Kaipeng Huang, Juan Huang, Shaogui Wang, Xiaoyan Shen, Peiqing Liu, Heqing Huang
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 381 Issue 1-2 Pg. 56-65 (Dec 05 2013) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 23896433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Fibronectins
• Free Radical Scavengers
• NF-kappa B
• Transforming Growth Factor beta1
• Berberine
• Intercellular Adhesion Molecule-1
• rho-Associated Kinases
• rhoA GTP-Binding Protein
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Active Transport, Cell Nucleus (drug effects)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Berberine (pharmacology)
• Cells, Cultured
• Diabetes Mellitus, Experimental (complications, metabolism)
• Drug Evaluation, Preclinical
• Fibronectins (genetics, metabolism)
• Free Radical Scavengers (pharmacology)
• Gene Expression (drug effects)
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Kidney (drug effects, pathology)
• Male
• Mesangial Cells (drug effects, metabolism)
• NF-kappa B (metabolism)
• Nephritis (drug therapy, etiology, metabolism)
• Oxidative Stress (drug effects)
• Protein Binding
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (genetics, metabolism)
• rho-Associated Kinases (metabolism)
• rhoA GTP-Binding Protein (metabolism)