title: TLR3 activation induces S100A7 to regulate keratinocyte differentiation after skin injury.
abstract: Human S100A7 (psoriasin) is highly expressed in psoriasis and other inflammatory diseases; however, the function of S100A7 in wound repair remains largely unknown. Here we demonstrated that skin injury increased the expression of S100A7. Damaged cells from wounded skin induced the expression of S100A7 via the activation of Toll-like receptor 3 (TLR3) followed by the activation of p38 MAPK. S100A7, in turn, acted on keratinocytes to induce the expression of terminal differentiation marker gene loricrin through the activation of p38 MAPK and caspase-1. The differentiation of keratinocytes induced by S100A7 resulted in skin stratification, thus efficiently promoting wound closure. Taken together, our results demonstrate that the activation of TLR3 accelerates wound closure via the induction of S100A7 to induce keratinocyte differentiation. These findings also provide new insights into the development of different forms of treatment with skin wounds.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Lei
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Chang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China. ylwu@bio.ecnu.edu.cn.
authors.forename: Yelin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China. yplai@bio.ecnu.edu.cn.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Lai
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C; D011119:Polynucleotides / Q000494:pharmacology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*; D012867:Skin / Q000293:injuries*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014945:Wound Healing; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D011119:Polynucleotides; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D048051:p38 Mitogen-Activated Protein Kinases; D020170:Caspase 1; D011070:Poly I-C
keywords: S100A7; TLR3; caspase-1; keratinocyte differentiation; wound closure