Role of integrin alpha8 in murine model of lung fibrosis.

Abstract

BACKGROUND:Integrin α8 (ITGA8) heterodimerizes with integrin β1 and is highly expressed in stromal cells of the lung. Platelet-derived growth factor receptor beta (PDGFRβ+) cells constitute a major population of contractile myofibroblasts in the lung following bleomycin-induced fibrosis. Integrin α8β1 is upregulated in fibrotic foci in bleomycin-induced lung injury. However, the functional role of ITGA8 in fibrogenesis has not been characterized. In this study, we examined whether genetic deletion of ITGA8 from PDGFRβ+ cells in the lung altered fibrosis. METHODS:Pdgfrb-Cre/+;Itga8flox/- or Pdgfrb-Cre/+;Itga8flox/flox (Cre+) and control mice (Cre-) were used for in vitro and in vivo studies. Primary cultures of PDGFRβ+ cells were exposed to TGFβ, followed by RNA isolation for qPCR. For in vivo studies, Cre+ and Cre- mice were characterized at baseline and after bleomycin-induced fibrosis. RESULTS:PDGFRβ-selected cells from Cre+ animals showed higher levels of Col1a1 expression after treatment with TGFβ. However, Cre- and Cre+ animals showed no significant difference in measures of acute lung injury or fibrosis following bleomycin challenge. CONCLUSION:While ITGA8 deletion in lung PDGFRβ+ stromal cells showed evidence of greater Col1a1 mRNA expression after TGFβ treatment in vitro, no functional difference was detected in vivo.