title: Identification of daidzein as a ligand of retinoic acid receptor that suppresses expression of matrix metalloproteinase-9 in HaCaT cells.
abstract: Retinoids have been used as therapeutics for diverse skin diseases, but their side effects limit clinical usage. Here, we report that extracts of two soybeans, Glycine max and Rhynchosia nulubilis, and their ethyl acetate fractions increased the transcriptional activity of retinoic acid receptors (RARs), and that daidzin and genistin were the major constituents of the active fractions. Daidzin and its aglycone, daidzein, induced transcriptional activity of RAR and RARγ. FRET analysis demonstrated that daidzein, but not daidzin, bound both RAR and RARγ with EC50 values of 28μM and 40μM, respectively. Daidzein increased expression of mRNA of RARγ through direct binding of RAR and recruitment of p300 to the RARγ2 promoter. Further, mRNA and gelatinolytic activity of matrix metalloproteinase-9 were decreased by daidzein in HaCaT cells. Together, these results indicate that daidzein functions as a ligand of RAR that could be a candidate therapeutic for skin diseases.
authors.affiliation: College of Pharmacy and Bio-MAX Institute, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hyeon-Jeong
authors.initials: HJ
authors.lastname: Oh
authors.forename: Young-Gyu
authors.initials: YG
authors.lastname: Kang
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Na
authors.forename: Hyeon-Ji
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jun Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
authors.forename: Mi-Ock
authors.initials: MO
authors.lastname: Lee
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008024:Ligands; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013025:Glycine max / Q000737:chemistry*; D015533:Transcriptional Activation / Q000187:drug effects; D000097768:Retinoic Acid Receptor gamma
chemical_list: D050881:E1A-Associated p300 Protein; D006131:Growth Inhibitors; D007529:Isoflavones; D008024:Ligands; D020780:Matrix Metalloproteinase 9; D010936:Plant Extracts; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000097768:Retinoic Acid Receptor gamma; C040641:genistin; C013908:daidzin; C004742:daidzein; C494360:EP300 protein, human
keywords: Daidzein; Ligand; Retinoic acid receptor; Skin