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FGF2 Overrides TGFβ1‐Driven Integrin ITGA11 Expression in Human Dermal Fibroblasts
Author(s) -
Grella Alexandra,
Kole Denis,
Holmes William,
Dominko Tanja
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25386
Subject(s) - extracellular matrix , microbiology and biotechnology , wound healing , fibroblast , integrin , extracellular , blot , chemistry , transforming growth factor , focal adhesion , biology , signal transduction , immunology , cell , biochemistry , in vitro , gene
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. J. Cell. Biochem. 117: 1000–1008, 2016. © 2015 Wiley Periodicals, Inc.