title: Panx1 regulates cellular properties of keratinocytes and dermal fibroblasts in skin development and wound healing.
abstract: Pannexin1 (Panx1), a channel-forming glycoprotein is expressed in neonatal but not in aged mouse skin. Histological staining of Panx1 knockout (KO) mouse skin revealed a reduction in epidermal and dermal thickness and an increase in hypodermal adipose tissue. Following dorsal skin punch biopsies, mutant mice exhibited a significant delay in wound healing. Scratch wound and proliferation assays revealed that cultured keratinocytes from KO mice were more migratory, whereas dermal fibroblasts were more proliferative compared with controls. In addition, collagen gels populated with fibroblasts from KO mice exhibited significantly reduced contraction, comparable to WT fibroblasts treated with the Panx1 blocker, probenecid. KO fibroblasts did not increase α-smooth muscle actin expression in response to TGF-β, as is the case for differentiating WT myofibroblasts during wound contraction. We conclude that Panx1 controls cellular properties of keratinocytes and dermal fibroblasts during early stages of skin development and modulates wound repair upon injury.
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada. Electronic address: spenuela@uwo.ca.
authors: Silvia
authors: S
authors: Penuela
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
authors: John J
authors: JJ
authors: Kelly
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada; Current address: Department of Medicine (Cardiology), Stanford School of Medicine, Stanford, California 94305, USA.
authors: Jared M
authors: JM
authors: Churko
authors: Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
authors: Kevin J
authors: KJ
authors: Barr
authors: Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
authors: Amy C
authors: AC
authors: Berger
authors: Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada; Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
authors: Dale W
authors: DW
authors: Laird
mesh_terms: D000199:Actins / Q000378:metabolism; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D015595:Skin Aging / Q000473:pathology / Q000502:physiology; D050151:Subcutaneous Fat / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000199:Actins; D000277:Adjuvants, Pharmaceutic; D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D016212:Transforming Growth Factor beta; D011339:Probenecid