Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 419, Issue C, Pages 72-82Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2015.10.001
Keywords
Farnesoid X receptor; Visfatin; Diabetic nephropathy; Mesangial cell
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Funding
- Natural Science Foundation of China [81270806, 31301167, 81270775]
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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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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