Myofibroblasts,recognized classically by-smooth muscle actin(-SMA)expression,play a key role in the wound-healing process,promoting wound closure and matrix deposition.Although a body of evidence shows that keratinocy...Myofibroblasts,recognized classically by-smooth muscle actin(-SMA)expression,play a key role in the wound-healing process,promoting wound closure and matrix deposition.Although a body of evidence shows that keratinocytes explanted onto a wound bed promote closure of a skin injury,the underlying mechanisms are not well understood.The basal layer of epidermis is rich in undifferentiated keratinocytes(UKs).We showed that UKs injected into granulation tissue could switch into-SMA positive cells,and accelerate the rate of skin wound healing.In addition,when the epidermis sheets isolated from foreskin cover up the wound bed or are induced in vitro,keratinocytes located at the basal layers or adjacent sites were observed to convert into myofibroblast-like cells.Thus,UKs have a potential for myofibroblastic transition,which provides a novel mechanism by which keratinocyte explants accelerate skin wound healing.展开更多
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 e...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.展开更多
基金supported in part by the National Natural Science Foundation of China(3127082,81230061,81121004,81201479)National Basic Research Program of China(2012CB518103,2012CB518105)National High Technology Research and Development Program of Ministry of Science and Technology of China(2011AA020113,2012AA020502,2013AA020105)
文摘Myofibroblasts,recognized classically by-smooth muscle actin(-SMA)expression,play a key role in the wound-healing process,promoting wound closure and matrix deposition.Although a body of evidence shows that keratinocytes explanted onto a wound bed promote closure of a skin injury,the underlying mechanisms are not well understood.The basal layer of epidermis is rich in undifferentiated keratinocytes(UKs).We showed that UKs injected into granulation tissue could switch into-SMA positive cells,and accelerate the rate of skin wound healing.In addition,when the epidermis sheets isolated from foreskin cover up the wound bed or are induced in vitro,keratinocytes located at the basal layers or adjacent sites were observed to convert into myofibroblast-like cells.Thus,UKs have a potential for myofibroblastic transition,which provides a novel mechanism by which keratinocyte explants accelerate skin wound healing.
基金supported by the National Natural Science Foundation of China (31170867, 31470878, 31222021,81202327)the Science and Technology Commission of Shanghai Municipality (13JC1402301, 11DZ2260300)Shanghai Education Commission (13SG25), and Henry Fok Educational Foundation (141017)
文摘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.
