FGF2 Overrides TGFβ1-Driven Integrin ITGA11 Expression in Human Dermal Fibroblasts

J Cell Biochem. 2016 Apr;117(4):1000-8. doi: 10.1002/jcb.25386. Epub 2015 Oct 6.


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.


Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Hypoxia
  • Cicatrix / genetics
  • Cicatrix / metabolism
  • Cicatrix / pathology
  • Cicatrix / prevention & control*
  • DNA Methylation / drug effects
  • Dermis / drug effects
  • Dermis / injuries
  • Dermis / metabolism
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / pharmacology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Focal Adhesions / drug effects
  • Gene Expression Regulation
  • Humans
  • Integrin alpha Chains / genetics*
  • Integrin alpha Chains / metabolism
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Oxygen / pharmacology
  • Primary Cell Culture
  • Re-Epithelialization / drug effects*
  • Re-Epithelialization / genetics
  • Signal Transduction
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism


  • FGF20 protein, human
  • ITGA11 protein, human
  • Integrin alpha Chains
  • Transforming Growth Factor beta1
  • Fibroblast Growth Factors
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Oxygen