Abstract
During alveolar repair, cuboidal type 2 alveolar epithelial progenitors rapidly proliferate and differentiate into flat type 1 alveolar epithelial cells. The mechanisms that regulate differentiation after injury may not recapitulate developmental programs as the timing, matrix, and degree of differentiation differs. We previously defined a role for epithelial-matrix interactions in lung organogenesis mediated by integrin extracellular matrix receptors. To test if β1-containing integrins are required during repair, we administered intratracheal lipopolysaccharide to mice with a post-developmental type 2 epithelial β1 deletion. Despite recoverable mild injury in littermate controls, β1-deficient mice repopulated the alveolus with abundant, rounded epithelial cells co-expressing type 2, type 1, and mixed intermediate cell state markers, but failed to differentiate into mature type 1 cells. With differentiation stalled, distal stem cell proliferation persisted with escalation of incompletely differentiated epithelial cells in late repair. These findings demonstrate that β1-containing integrins are exquisitely required for terminal epithelial differentiation post-injury.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
The authors have declared that no conflict of interest exists.
Introduction and discussion revised.