Role of integrin alpha8 in murine model of lung fibrosis

Background Integrin a8 (ITGA8) heterodimerizes with integrin beta 1 and is highly expressed in stromal cells of the lung. Platelet-derived growth factor receptor beta (PDGFR beta+) cells constitute a major population of contractile myofibroblasts in the lung following bleomycin-induced fibrosis. Integrin alpha 8 beta 1 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 PDGFR beta+ cells in the lung altered fibrosis. Methods Pdgfrb-Cre/+; Itga8(flox/-)or Pdgfrb-Cre/+; Itga8(flox/flox) (Cre+) and control mice (Cre-) were used for in vitro and in vivo studies. Primary cultures of PDGFR beta+ cells were exposed to TGF beta, followed by RNA isolation for qPCR. For in vivo studies, Cre+ and Cre-mice were characterized at baseline and after bleomycin-induced fibrosis. Results PDGFR beta-selected cells from Cre+ animals showed higher levels of Col1a1 expression after treatment with TGF beta. 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 PDGFR beta+ stromal cells showed evidence of greater Col1a1 mRNA expression after TGF beta treatment in vitro, no functional difference was detected in vivo.