Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 381, Issue 1-2, Pages 56-65Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2013.07.019
Keywords
Diabetic nephropathy; Berberine; RhoA/ROCK; NF-kappa B; Fibronectin
Categories
Funding
- National Natural Science Foundation of China [81170676]
- Science, Technology Program of Guangdong province, PR China [2011A080502004]
- Guangdong Science and Technology Correspondent of Enterprise Foundation [2011B090600033]
- Guangdong Natural Science Foundation [2012020010991]
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The accumulation of glomerular extracellular matrix proteins, especially fibronectin (FN), is a critical pathological characteristic of diabetic renal fibrosis. Inflammation mediated by nuclear factor-kappa B (NF-kappa B) plays a critical role in the pathogenesis of diabetic nephropathy (DN). RhoA/ROCK signaling is responsible for FN accumulation and NF-kappa B 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-kappa B 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-kappa B 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. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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