Discovering The Developmental Origins of Obesity

The Polish Academy of Sciences in Olsztyn, Poland

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Scarless skin wound healing in FOXN1 deficient (nude) mice is associated with distinctive matrix metalloproteinase expression

Barbara Gawronska-Kozak1

Regenerative Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA
Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Poland

Keywords: Matrix metalloproteinases, Wound healing, Regeneration, FOXN1, Nude mice

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.

Matrix Biology 30 (2011) 290–300

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1 Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Poland, ul. Tuwima 10, 10-747 Olsztyn, Poland. Tel.: +48 89 5234621; fax: +48 89 5240124. E-mail address: This e-mail address is being protected from spambots. You need JavaScript enabled to view it. .

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