PT  - JOURNAL ARTICLE
AU  - Bernadette Gochuico
AU  - Jennifer Wang
AU  - Lily Smith
AU  - Jasmina Abdalla
AU  - Meixing Zuo
AU  - Tesiya Franklin
AU  - Shachar Abudi
AU  - Resat Cinar
AU  - May Malicdan
AU  - Chen Han
TI  - Pro-fibrotic phenotype of human Hermansky-Pudlak syndrome lung fibroblasts
AID  - 10.1183/13993003.congress-2021.PA3613
DP  - 2021 Sep 05
TA  - European Respiratory Journal
PG  - PA3613
VI  - 58
IP  - suppl 65
4099  - http://erj.ersjournals.com/content/58/suppl_65/PA3613.short
4100  - http://erj.ersjournals.com/content/58/suppl_65/PA3613.full
SO  - Eur Respir J2021 Sep 05; 58
AB  - Hermansky-Pudlak syndrome type 1 (HPS-1) is associated with highly prevalent pulmonary fibrosis. Patients with HPS-1 usually manifest with pulmonary fibrosis in middle-age and are typically younger than patients with idiopathic pulmonary fibrosis (IPF). Given the accelerated onset of pulmonary fibrosis in HPS-1, we hypothesized that lung fibroblasts from individuals with HPS-1 pulmonary fibrosis are constitutively activated and have an enhanced fibrotic response. To test this hypothesis, fibroblasts cultured from explanted lung tissue from patients with HPS-1 pulmonary fibrosis were analyzed and compared to lung fibroblasts from patients with IPF and normal controls. We found that HPS-1 lung fibroblasts express high levels of alpha-smooth muscle actin (a-SMA) transcript and protein compared to normal lung fibroblasts. Similarly, levels of connective tissue growth factor (CTGF) were increased in HPS-1 lung fibroblasts compared to normal cells. In contrast, no significant differences in a-SMA or CTGF protein levels were found in IPF and normal lung fibroblasts. Immunostaining of lung tissue showed prominent expression of a-SMA and CTGF in alveolar interstitial lung fibroblasts and myofibroblasts from patients with HPS-1 pulmonary fibrosis or IPF compared to normal lung. Levels of fibronectin, collagen type I α1, and collagen type I α2 transcripts were significantly higher in HPS-1 lung fibroblasts stimulated with transforming growth factor (TGF)-b compared to those in HPS-1 lung fibroblasts incubated with vehicle-only or normal lung fibroblasts stimulated with TGF-b. In conclusion, HPS-1 lung fibroblasts are constitutively activated and exhibit an exaggerated fibrotic response when stimulated with TGF-b.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3613.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).