title: 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.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Baoshang
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Zhexue
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu 610083, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Zhengmin
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: yuanfh023@126.com.
authors.forename: Fahuan
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: mujiaotmmu@126.com.
authors.forename: Jiao
authors.initials: J
authors.lastname: Mu
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D016207:Cytokines; D007555:Isoxazoles; D054409:Nicotinamide Phosphoribosyltransferase; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C085455:nicotinamide phosphoribosyltransferase, human; C412815:GW 4064
keywords: Diabetic nephropathy; Farnesoid X receptor; Mesangial cell; Visfatin