期刊
JCI INSIGHT
卷 8, 期 14, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.167211
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During alveolar repair, the proliferation and differentiation of alveolar type 2 epithelial cell progenitors into flat alveolar type 1 epithelial cells are essential. The presence of β1-containing integrins is crucial for functional alveolar repair and terminal epithelial differentiation. Failure of β1 integrin leads to severe inflammation, emphysema, increased proliferation of AT2 cells, and impaired differentiation into mature AT1 cells.
During alveolar repair, alveolar type 2 (AT2) epithelial cell progenitors rapidly proliferate and differentiate into flat AT1 epithelial cells. Failure of normal alveolar repair mechanisms can lead to loss of alveolar structure (emphysema) or development of fibrosis, depending on the type and severity of injury. To test if & beta;1-containing integrins are required during repair following acute injury, we administered E. coli lipopolysaccharide (LPS) by intratracheal injection to mice with a postdevelopmental deletion of & beta;1 integrin in AT2 cells. While control mice recovered from LPS injury without structural abnormalities, & beta;1-deficient mice had more severe inflammation and developed emphysema. In addition, recovering alveoli were repopulated with an abundance of rounded epithelial cells coexpressing AT2 epithelial, AT1 epithelial, and mixed intermediate cell state markers, with few mature type 1 cells. AT2 cells deficient in & beta;1 showed persistently increased proliferation after injury, which was blocked by inhibiting NF-KB activation in these cells. Lineage tracing experiments revealed that & beta;1-deficient AT2 cells failed to differentiate into mature AT1 epithelial cells. Together, these findings demonstrate that functional alveolar repair after injury with terminal alveolar epithelial differentiation requires & beta;1-containing integrins.
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