title: Novel naphthochalcone derivative accelerate dermal wound healing through induction of epithelial-mesenchymal transition of keratinocyte.
abstract: BACKGROUND
  Wound healing is an intricate process whereby the skin repairs itself after injury. The epithelial-mesenchymal transition (EMT) is associated with wound healing and tissue regeneration. Naphthochalcone derivatives have various pharmaceutical properties. We investigated the effect of a novel naphthochalcone derivative, 2-(5-(2,4,6-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol (TDPN), on dermal wound healing in vivo and the migration of keratinocytes in vitro.
  
  
  RESULTS
  We investigated the effect of TDPN on signaling pathway and epithelial-mesenchymal transition through protein and transcriptional expression. The TDPN treatment accelerated dermal closure about 3 days and remodeling of dermis. We found that treatment with TDPN induced the migration of keratinocytes but not cytotoxicity. TDPN induced the phosphorylation of ERK and AKT. TDPN-treated cells showed loss of adherence protein and showed induction of the transcriptional factor Slug, mesenchymal marker, and fibronectin. Moreover, TDPN treatment induced the expression of matrix metalloproteinase-1 (MMP-1), which degrades specific components of the extracellular matrix, thereby providing new substrates that facilitate migration and invasion. MMP expression is considered to be one of the major attributes acquired by cells after EMT.
  
  
  CONCLUSIONS
  We propose that a novel naphthochalcone derivative TDPN is capable of promoting keratinocyte migration via the induction of EMT resulting acceleration of wound closure and matrix remodeling.
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, 690-756, South Korea.
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Seo
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, 690-756, South Korea.
authors.forename: Manh Tin
authors.initials: MT
authors.lastname: Ho
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, 690-756, South Korea.
authors.forename: Ngoc Thuy
authors.initials: NT
authors.lastname: Bui
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, 690-756, South Korea.
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Applied Chemistry, Dongduk Women's University, Seoul, 136-714, South Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Koh
authors.affiliation: Division of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, South Korea.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Pathology, School of Medicine, Jeju National University, Jeju, 690-756, South Korea.
authors.forename: Changlim
authors.initials: C
authors.lastname: Hyun
authors.affiliation: Department of Biochemistry School of Medicine, Jeju National University, Jeju, 690-756, South Korea. moonjcho@jejunu.ac.kr.|Institute of Medical Science, Jeju National University, Jeju, 690-756, South Korea. moonjcho@jejunu.ac.kr.
authors.forename: Moonjae
authors.initials: M
authors.lastname: Cho
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics*; D009281:Naphthalenes / Q000008:administration & dosage; D009284:Naphthols / Q000008:administration & dosage*; D010766:Phosphorylation; D011720:Pyrazoles / Q000008:administration & dosage*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects* / Q000235:genetics
chemical_list: C000605838:2-(5-(2,4,6-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol; D009281:Naphthalenes; D009284:Naphthols; D011720:Pyrazoles; C118253:naphthocyclinone; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1