November 15, 2017

Radiation and pulmonary fibrosis

To develop strategies for preventing radiation-induced lung fibrosis (scarring), Vanderbilt investigators are exploring the cell types and factors that contribute to the fibrotic response.

Radiation-induced pulmonary fibrosis — tissue scarring that can permanently impair lung function — limits the delivery of therapeutic radiation doses to non-small cell lung cancer.

To develop strategies for preventing or reducing fibrosis, Michael Freeman, Ph.D., and colleagues are exploring the cell types and factors that contribute to the radiation-induced fibrotic response.

The investigators previously showed that loss of the transcription factor Nrf2 increases susceptibility to pulmonary fibrosis. They now show that thoracic (chest) radiation of mice causes a loss of alveolar type 2 cells and that this loss is enhanced in mice lacking Nrf2.

The researchers found that a specific stem/progenitor cell population was inhibited following radiation in mice missing Nrf2, and that alveolar type 2 cells in these mice were more likely to change into myofibroblasts — a cell type implicated in fibrosis.

The findings, reported in the November Free Radical Biology and Medicine, demonstrate that Nrf2 participates in stem cell mobilization and helps maintain the alveolar type 2 cell reparative process in injured lungs.

This study was supported in part by grants from the National Instittues of Health (HL112286, CA093240, CA152601, CA152799, CA168292, CA214025, CA068485).

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