title: Scarless skin wound healing in FOXN1 deficient (nude) mice is associated with distinctive matrix metalloproteinase expression.
abstract: Similar to mammalian fetuses FOXN1 deficient (nude) mice are able to restore the structure and integrity of injured skin in a scarless healing process by mechanisms independent of the genetic background. Matrix metalloproteinases (MMPs) are required for regular skin wound healing and the distinctive pattern of their expression has been implicated to promote scarless healing. In this study, we analyzed the temporal and spatial expression patterns of these molecules during the incisional skin wounds in adult nude mice. Macroscopic and histological analyses of skin wounds revealed an accelerated wound healing process, minimal granulation tissue formation and markedly diminished scarring in nude mice. Quantitative RT-PCR (Mmp-2, -3, -8, -9, -10, -12, -13, -14 and Timp-1, -2, -3), Western blots (MMP-13) and gelatin zymography (MMP-9) revealed that MMP-9 and MMP-13 showed a unique, bimodal pattern of up-regulation during the early and late phases of wound healing in nude mice. Immunohistochemically MMP-9 and MMP-13 were generally detected in epidermis during the early phase and in dermis during the late (remodeling) phase. Consistent with these in vivo observations, dermal fibroblasts cultured from nude mice expressed higher levels of types I and III collagen, MMP-9 and MMP-13 mRNA levels and higher MMP enzyme activity than wild type controls. Collectively, these finding suggest that the bimodal pattern of MMP-9 and MMP-13 expression during skin repair process in nude mice could be a major component of their ability for scarless healing.
authors.affiliation: Regenerative Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA. b.kozak@pan.olsztyn.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Gawronska-Kozak
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D057075:Enzyme Assays; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000172:deficiency* / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D051858:Forkhead Transcription Factors; D019714:Tissue Inhibitor of Metalloproteinases; C090140:Whn protein; D003094:Collagen; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507081:Mmp13 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse