title: Induction of nephrin gene expression by selective cooperation of the retinoic acid receptor and the vitamin D receptor.
abstract: BACKGROUND
  Nephrin is a key molecule involved in the structure and function of the slit diaphragm in the glomerulus. We previously reported that all-trans retinoic acid (ATRA) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induced expression of nephrin in murine podocytes. In this report, we investigated roles of the retinoic acid receptor (RAR), the retinoid X receptor (RXR) and the vitamin D receptor (VDR) in the regulation of the nephrin gene.
  
  
  METHODS
  Reporter podocytes were treated with agonists and/or antagonists of RAR, RXR or VDR, and activities of the nephrin gene promoter, the retinoic acid response element (RARE) and the vitamin D response element (VDRE) were evaluated.
  
  
  RESULTS
  Expression of nephrin in podocytes was up-regulated by ATRA and 1,25(OH)(2)D(3). The nephrin gene promoter was also activated by these agents, which was mediated by RAR and VDR, but unexpectedly, not by RXR. ATRA-triggered, RAR-mediated activation of the nephrin gene promoter was not suppressed by the VDR antagonist. Similarly, ATRA-induced activation of RARE was not inhibited by the VDR antagonist. In contrast, the 1,25(OH)(2)D(3)-triggered, VDR-mediated activation of the nephrin gene promoter was significantly suppressed by the RAR antagonist, but not by RXR antagonists. Interestingly, 1,25(OH)(2)D(3)-induced activation of VDRE was not inhibited by the RAR antagonist.
  
  
  CONCLUSIONS
  These results suggested selective cooperation of RAR and VDR in the regulation of the nephrin gene, i.e. (1) ATRA induces nephrin gene expression via RAR independently of RXR and VDR and (2) 1,25(OH)(2)D(3) induces nephrin gene expression via selective cooperation of RAR and VDR, which is independent of RXR.
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Maro
authors.initials: M
authors.lastname: Okamura
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Takano
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Saito
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D050199:Podocytes / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; C113267:nephrin