Role of integrin alpha8 in murine model of lung fibrosis.

PLoS One

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.

Published: November 2018

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973593PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197937PLOS

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