Open AccessRole of integrin alpha8 in murine model of lung fibrosis
Author(s) -
Chi F. Hung,
Carole L. Wilson,
YuHua Chow,
Lynn M. Schnapp
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0197937
Subject(s) - ctgf , bleomycin , fibrosis , pulmonary fibrosis , biology , lung , cancer research , pdgfrb , stromal cell , population , platelet derived growth factor receptor , pathology , myofibroblast , medicine , receptor , growth factor , biochemistry , genetics , environmental health , chemotherapy , gene
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/+; 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 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 .