title: TMF and glycitin act synergistically on keratinocytes and fibroblasts to promote wound healing and anti-scarring activity.
abstract: Keratinocyte-fibroblast interactions are critical for skin repair after injury. During the proliferative phase of wound healing, proliferation, migration and differentiation of these cells are the major mechanisms leading to tissue remodeling. We have previously reported that glycitin, a major soy isoflavone, stimulates dermal fibroblast proliferation; and the phytochemical, 4',6,7-trimethoxyisoflavone (TMF), induces migration of HaCaT keratinocyte cells. We therefore investigated whether these compounds display synergistic effects on skin cells during wound healing in vitro and in vivo. Co-treatment with TMF and glycitin synergistically promotes the proliferation and migration of both keratinocytes and dermal fibroblasts, with a 1:1 ratio of these compounds showing the greatest efficacy in our co-culture system. This keratinocyte-fibroblast interaction occurred via the secretion of TGF-β, and the induction of differentiation and proliferation was confirmed in both indirect and direct co-culture assays. In an excisional and burn wound animal model, mice treated with a 1:1 ratio of TMF and glycitin showed faster wound closure, regeneration and scar reduction than even the positive control drug. These data indicate that two isoflavones, TMF and glycitin, act synergistically to promote wound healing and anti-scarring and could potentially be developed together as a bioactive therapeutic for wound treatment.
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Seo
authors.affiliation: Division of Bioscience and Biotechnology, Konkuk University, Seoul, Korea.
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Applied Chemistry, Dongduk Women's University, Seoul, Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Koh
authors.affiliation: Department of Urology, School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Huh
authors.affiliation: Department of Pathology, School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Changlim
authors.initials: C
authors.lastname: Hyun
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, Korea.|Institute of Medical Science, Jeju National University, Jeju, Korea.
authors.forename: Moonjae
authors.initials: M
authors.lastname: Cho
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000188:drug therapy*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR
chemical_list: C000593593:4',6,7-trimethoxyisoflavone; D007529:Isoflavones; D008233:Lymphotoxin-alpha; C433283:glycitin