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Novel naphthochalcone derivative accelerate dermal wound healing through induction of epithelial-mesenchymal transition of keratinocyte.
- Source :
-
Journal of biomedical science [J Biomed Sci] 2015 Jul 01; Vol. 22, pp. 47. Date of Electronic Publication: 2015 Jul 01. - Publication Year :
- 2015
-
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.<br />Result: 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.<br />Conclusion: 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.
- Subjects :
- Animals
Cell Movement drug effects
Extracellular Matrix drug effects
Extracellular Matrix metabolism
Gene Expression Regulation drug effects
Humans
Keratinocytes metabolism
Keratinocytes pathology
Matrix Metalloproteinase 1 biosynthesis
Naphthalenes administration & dosage
Phosphorylation
Rats
Signal Transduction drug effects
Skin drug effects
Skin pathology
Wound Healing genetics
Epithelial-Mesenchymal Transition drug effects
Keratinocytes drug effects
Matrix Metalloproteinase 1 genetics
Naphthols administration & dosage
Pyrazoles administration & dosage
Wound Healing drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0127
- Volume :
- 22
- Database :
- MEDLINE
- Journal :
- Journal of biomedical science
- Publication Type :
- Academic Journal
- Accession number :
- 26130135
- Full Text :
- https://doi.org/10.1186/s12929-015-0141-3