December 10, 2012

Genetic clues to lung scarring

A rare genetic syndrome provides new clues to lung scarring (pulmonary fibrosis), a potentially deadly consequence of many lung diseases.

Pulmonary fibrosis (the scarring of lung tissue) is a potentially deadly consequence of many lung diseases. Therapies are limited due to incomplete understanding of fibrotic mechanisms. Hermansky-Pudlak syndrome (HPS), a genetic disorder resulting in pulmonary fibrosis, offers a model for studying the disease process.


Using several HPS genetic mouse models, Lisa Young, M.D., associate professor of Pediatrics, and colleagues have found that HPS lung fibrosis originates from impaired intracellular trafficking specifically in surfactant-producing cells lining the lung’s air sacs (alveolar epithelial cells). They report, in the Nov. 15 issue of the American Journal of Respiratory and Critical Care Medicine, that susceptibility to drug-induced fibrosis in HPS mice mirrors the genotype-specific fibrosis in HPS patients. Further, even though HPS genetic mutations affect numerous cell types, correction of the defect only in the lung epithelial cells protected HPS mice from experimental fibrosis.

The findings provide new insights into the mechanisms of pulmonary fibrosis, which could inform the development of preventive and treatment strategies.

The research was supported by grants from the National Heart, Lung and Blood Institute (HL082757, HL085317, HL092870, HL068861), the American Thoracic Society, the Parker B. Francis Foundation and the Department of Veterans Affairs.