Activation of farnesoid X receptor downregulates visfatin and attenuates diabetic nephropathy.

Abstract

Visfatin, a recently discovered adipocytokine, has been shown to have an important role in the pathogenesis of diabetic nephropathy (DN). The farnesoid X receptor (FXR), a ligand-activated nuclear receptor, plays a protective role in DN. The regulation between FXR and visfatin and their interaction in DN has not been well established. In this study, we reported that FXR agonist GW4064 reduced high glucose induced human mesangial cells (HMCs) inflammation, fibrosis and proliferation by downregulating visfatin expression, which can be blunted by exogenous visfatin treatment. Moreover, luciferase reporter assay showed FXR regulated visfatin transcription activity probably by binding to the -1607 bp and -1192 bp region of the visfatin promoter. In vivo study also showed that GW4064 ameliorated the progression of DN in db/db mice with a decreased visfatin expression. These findings suggest that FXR activation delayed the progression of diabetic nephropathy and this effect is through downregulating visfatin.

• Authors: Baoshang Zhou, Bing Feng, Zhexue Qin, Youguang Zhao, Yu Chen, Zhengmin Shi, Yi Gong, Jing Zhang, Fahuan Yuan, Jiao Mu
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 419 Pg. 72-82 (Jan 05 2016) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 26450152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Cytokines
• Isoxazoles
• Receptors, Cytoplasmic and Nuclear
• farnesoid X-activated receptor
• Nicotinamide Phosphoribosyltransferase
• nicotinamide phosphoribosyltransferase, human
• GW 4064

Topics

• Animals
• Cell Line
• Cell Proliferation (drug effects)
• Cytokines (genetics, metabolism)
• Diabetic Nephropathies (drug therapy, genetics, metabolism)
• Disease Models, Animal
• Gene Expression Regulation (drug effects)
• Humans
• Isoxazoles (administration & dosage, pharmacology)
• Male
• Mesangial Cells (cytology, drug effects)
• Mice
• Nicotinamide Phosphoribosyltransferase (genetics, metabolism)
• Promoter Regions, Genetic (drug effects)
• Receptors, Cytoplasmic and Nuclear (agonists, genetics, metabolism)
• Transcription, Genetic (drug effects)