title: Integrin β1 is required for dermal homeostasis.
abstract: Integrins are heterodimers that mediate cell attachment to the extracellular matrix. Previously, we used fibroblast-specific knockout mice to show that the integrin β1 subunit was required in vivo for dermal fibrogenesis and cutaneous tissue repair. Here, we show that integrin β1 expression by fibroblasts is required for dermal homeostasis; at 8 weeks after deletion of integrin β1, the dermis is significantly thinner, expressing less collagen and displaying reduced generation of reactive oxygen species (ROS). Cultured integrin β1-deficient fibroblasts show reduced rac1 activation and ROS generation. Overexpressing rac1 in integrin β1-deficient fibroblasts restored ROS generation; adding hydrogen peroxide to integrin β1-deficient fibroblasts restored Col1a2 (collagen, type I, α2) and α-smooth muscle actin (α-SMA) mRNA expression and α-SMA protein expression and stress fiber formation. Thus integrin β1 expression by fibroblasts is required for the maintenance of dermal connective tissue via a rac/ROS pathway.
authors.affiliation: Department of Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Shangxi
authors.initials: S
authors.lastname: Liu
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000166:cytology* / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein
chemical_list: D024042:Collagen Type I; D019012:Integrin beta1; D009479:Neuropeptides; D016877:Oxidants; C484602:Rac1 protein, mouse; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein