title: Mechanical tension and integrin alpha 2 beta 1 regulate fibroblast functions.
abstract: The extracellular matrix (ECM) environment in connective tissues provides fibroblasts with a structural scaffold and modulates cell shape, but it also profoundly influences the fibroblast phenotype. Here we studied fibroblasts cultured in a three-dimensional network of native collagen, which was either mechanically stressed or relaxed. Mechanical load induces fibroblasts that synthesize abundant ECM and a characteristic array of cytokines/chemokines. This phenotype is reminiscent of late granulation tissue or scleroderma fibroblasts. By contrast, relaxed fibroblasts are characterized by induction of proteases and a subset of cytokines that does not overlap with that of mechanically stimulated cells. Thus, the biochemical composition and physical nature of the ECM exert powerful control over the phenotypes of fibroblasts, ranging from "synthetic" to "inflammatory" phenotypes. Interactions between fibroblasts and collagen fibrils are mostly mediated by a subset of beta 1 integrin receptors. Fibroblasts utilize alpha 1 beta 1, alpha 2 beta 1, and alpha 11 beta 1 integrins for establishing collagen contacts and transducing signals. In vitro assays and mouse genetics have demonstrated individual tasks served by each receptor, but also functional redundancy. Unraveling the integrated functions of fibroblasts, collagen integrin receptors, collagen fibrils, and mechanical tension will be important to understand the molecular mechanisms underlying tissue repair and fibrosis.
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Eckes
authors.forename: Manon C
authors.initials: MC
authors.lastname: Zweers
authors.forename: Zhi Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Ralf
authors.initials: R
authors.lastname: Hallinger
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Monique
authors.initials: M
authors.lastname: Aumailley
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000502:physiology*; D051379:Mice; D010641:Phenotype; D012595:Scleroderma, Systemic / Q000378:metabolism; D013314:Stress, Mechanical; D014945:Wound Healing / Q000502:physiology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D038982:Integrin alpha2beta1; D051546:Cyclooxygenase 2