title: FGF2 Overrides TGFβ1-Driven Integrin ITGA11 Expression in Human Dermal Fibroblasts.
abstract: Deposition of collagen-based extracellular matrix by fibroblasts during wound healing leads to scar formation--a typical outcome of the healing process in soft tissue wounds. The process can, however, be skewed in favor of tissue regeneration by manipulation of wound environment. Low oxygen conditions and supplementation with FGF2 provide extracellular cues that drive wound fibroblasts towards a pro-regenerative phenotype. Under these conditions, fibroblasts dramatically alter expression of many genes among which the most significantly deregulated are extracellular matrix and adhesion molecules. Here we investigate the mechanism of a collagen I binding integrin α11 (ITGA11) deregulation in response to low oxygen-mediated FGF2 effects in dermal fibroblasts. Using RT-PCR, qRT-PCR, Western blotting, and immunocytochemistry, we describe significant down-regulation of ITGA11. Decrease in ITGA11 is associated with its loss from focal adhesions. We show that loss of ITGA11 requires FGF2 induced ERK1/2 activity and in the presence of FGF2, ITGA11 expression cannot be rescued by TGFβ1, a potent activator of ITGA11. Our results indicate that FGF2 may be redirecting fibroblasts towards an anti-fibrotic phenotype by overriding TGFβ1 mediated ITGA11 expression.
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts, 01609.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Grella
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts, 01609.
authors.forename: Denis
authors.initials: D
authors.lastname: Kole
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts, 01609.
authors.forename: William
authors.initials: W
authors.lastname: Holmes
authors.affiliation: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, Massachusetts, 01609.|Center for Biomedical Sciences and Engineering, University of Nova Gorica, Nova Gorica 5000, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Dominko
mesh_terms: D015687:Cell Hypoxia; D002921:Cicatrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019175:DNA Methylation / Q000187:drug effects; D020405:Dermis / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D022001:Focal Adhesions / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D061251:Primary Cell Culture; D062326:Re-Epithelialization / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C416003:FGF20 protein, human; C121535:ITGA11 protein, human; D039001:Integrin alpha Chains; D053773:Transforming Growth Factor beta1; D005346:Fibroblast Growth Factors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010100:Oxygen
keywords: FIBROBLAST; FIBROBLAST GROWTH FACTOR; HYPOXIA; INTEGRIN ITGA11; TRANSFORMING GROWTH FACTOR β