Hypoxia-Inducible Factor 1 α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury.

Hypoxia-Inducible Factor 1α Signaling Promotes Repair of the Alveolar Epithelium after Acute Lung Injury. Am J Pathol. 2017 Jun 12;: Authors: McClendon J, Jansing NL, Redente EF, Gandjeva A, Ito Y, Colgan SP, Ahmad A, Riches DWH, Chapman HA, Mason RJ, Tuder RM, Zemans RL Abstract During acute respiratory distress syndrome, epithelial cells, primarily alveolar type (AT) I cells, die and slough off the basement membrane, resulting in enhanced permeability. ATII cells proliferate and spread onto the denuded basement membrane to reseal the barrier. Repair of the alveolar epithelium is critical for clinical recovery; however, the mechanisms underlying ATII cell proliferation and spreading are not well understood. We hypothesized that hypoxia-inducible factor (HIF)1α promotes proliferation and spreading of ATII cells during repair after lung injury. Mice were treated with intratracheal lipopolysaccharide or hydrochloric acid. HIF activation in ATII cells after injury was demonstrated by increased luciferase activity in oxygen degradation domain-Luc (HIF reporter) mice and expression of the HIF1α target gene GLUT1. ATII cell proliferation during repair after lung injury was attenuated in ATII cell-specific HIF1α knockout (SftpcCreERT2(+/-);HIF1α(f/f)) mice. The HIF target vascular endothelial growth factor promoted ATII cell proliferation in vitro and after lung injury in vivo. In the scratch wound assay of cell spreading, HIF stabil...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research