title: Topical application of ALK5 inhibitor A-83-01 reduces burn wound contraction in rats by suppressing myofibroblast population.
abstract: Burn scar contracture that follows the healing of deep dermal burns causes severe deformation and functional impairment. However, its current therapeutic interventions are limited with unsatisfactory outcomes. When we treated deep second-degree burns in rat skin with activin-like kinase 5 (ALK5) inhibitor A-83-01, it reduced wound contraction and enhanced the area of re-epithelialization so that the overall time for wound closing was not altered. In addition, it reduced myofibroblast population in the dermis of burn scar with a diminished deposition of its biomarker proteins such as α-SMA and collagen. Treatment of rat dermal fibroblast with A-83-01 inhibited transforming growth factor-β1 (TGF-β1)-dependent induction of α-SMA and collagen type I. Taken together, these results suggest that topical application of ALK5 inhibitor A-83-01 could be effective in preventing the contraction of burn wound without delaying the wound closure by virtue of its inhibitory activity against the TGF-β-induced increase of myofibroblast population.
authors.affiliation: a Chemical Kinomics Research Center , Korea Institute of Science and Technology , Seoul , Korea.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.forename: Yang-Hyun
authors.initials: YH
authors.lastname: Kim
authors.forename: Trong Nhat
authors.initials: TN
authors.lastname: Phan
authors.forename: Beom-Seok
authors.initials: BS
authors.lastname: Yang
mesh_terms: D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D002056:Burns / Q000188:drug therapy*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D023421:Models, Animal; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D013882:Thiosemicarbazones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: C507011:A-83-01; D011720:Pyrazoles; D018125:Receptors, Transforming Growth Factor beta; D013882:Thiosemicarbazones; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat
keywords: A-83-01; ALK5 inhibitor; TGF-β signaling; burn wound contraction; myofibroblast