Identification of daidzein as a ligand of retinoic acid receptor that suppresses expression of matrix metalloproteinase-9 in HaCaT cells

Hyeon-Jeong Oh; Young-Gyu Kang; Tae-Young Na; Hyeon-Ji Kim; Jun Seong Park; Won-Jea Cho; Mi-Ock Lee

doi:10.1016/j.mce.2013.06.015

Identification of daidzein as a ligand of retinoic acid receptor that suppresses expression of matrix metalloproteinase-9 in HaCaT cells

Mol Cell Endocrinol. 2013 Aug 25;376(1-2):107-13. doi: 10.1016/j.mce.2013.06.015. Epub 2013 Jun 19.

Authors

Hyeon-Jeong Oh¹, Young-Gyu Kang, Tae-Young Na, Hyeon-Ji Kim, Jun Seong Park, Won-Jea Cho, Mi-Ock Lee

Affiliation

¹ College of Pharmacy and Bio-MAX Institute, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.

PMID: 23791815
DOI: 10.1016/j.mce.2013.06.015

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.

Keywords: Daidzein; Ligand; Retinoic acid receptor; Skin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Cell Line
E1A-Associated p300 Protein / genetics
E1A-Associated p300 Protein / metabolism
Gene Expression / drug effects
Glycine max / chemistry*
Growth Inhibitors / chemistry
Growth Inhibitors / isolation & purification
Growth Inhibitors / pharmacology*
Humans
Isoflavones / chemistry
Isoflavones / isolation & purification
Isoflavones / pharmacology*
Keratinocytes / cytology
Keratinocytes / drug effects*
Keratinocytes / metabolism
Ligands
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism*
Molecular Docking Simulation
Plant Extracts / chemistry
Promoter Regions, Genetic
Protein Binding
RNA, Messenger / genetics
RNA, Messenger / metabolism*
Receptors, Retinoic Acid / chemistry*
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / metabolism
Retinoic Acid Receptor gamma
Transcriptional Activation / drug effects

Substances

Growth Inhibitors
Isoflavones
Ligands
Plant Extracts
RNA, Messenger
Receptors, Retinoic Acid
genistin
daidzin
daidzein
E1A-Associated p300 Protein
EP300 protein, human
Matrix Metalloproteinase 9