Role of integrin alpha8 in murine model of lung fibrosis.

ABSTRACT:

Background

Integrin ?8 (ITGA8) heterodimerizes with integrin ?1 and is highly expressed in stromal cells of the lung. Platelet-derived growth factor receptor beta (PDGFR?+) cells constitute a major population of contractile myofibroblasts in the lung following bleomycin-induced fibrosis. Integrin ?8?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?+ 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 PDGFR?+ cells were exposed to TGF?, 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?-selected cells from Cre+ animals showed higher levels of Col1a1 expression after treatment with TGF?. 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?+ stromal cells showed evidence of greater Col1a1 mRNA expression after TGF? treatment in vitro, no functional difference was detected in vivo.

SUBMITTER: Hung CF 

PROVIDER: S-EPMC5973593 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature