RT Journal Article SR Electronic T1 DHEA has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP erj00274-2012 DO 10.1183/09031936.00027412 A1 Criselda Mendoza A1 Ana Valero Jiménez A1 Claudia Rangel A1 Alfredo Lozano A1 Violeta Morales A1 Carina Becerril A1 Roberto Chavira A1 Víctor Ruiz A1 Lourdes Barrera A1 Martha Montaño A1 Annie Pardo A1 Moisés Selman YR 2012 UL http://erj.ersjournals.com/content/early/2012/10/25/09031936.00027412.abstract AB Idiopathic pulmonary fibrosis (IPF) is an aging-related lung disorder characterized by expansion of the myofibroblast population and aberrant lung remodeling. Dehydroepiandrosterone (DHEA), a steroid pro-hormone, decreases with age but an exaggerated decline has been associated with chronic-degenerative diseases.We quantified the plasma levels of DHEA and its sulfated form (DHEA-S) in 137 IPF patients and 58 controls and examined the effects of DHEA on human lung fibroblasts.Plasmatic DHEA/DHEA-S were significantly decreased in male IPF patients, (DHEA, median (max-min): 4.4 (0.2–29.2) versus 6.7 (2.1–15.2) ng·mL−1; p<0.01; DHEA-S, median: 47 (15.0–211) versus 85.2 (37.6–247.0) μg·dl−1; p<0.001), while in females only DHEA-S was significantly decreased (median: 32.6 (15.0–303.0) versus 68.3 (16.4-171); p<0.001). DHEA caused a decrease of fibroblast proliferation and a ∼2-fold increase of fibroblast apoptosis, likely through the intrinsic pathway with activation of caspase-9. This effect was accompanied by upregulation of several pro-apoptotic proteins (Bax and cyclin-dependent kinase-inhibitor CDNK1A) and downregulation of anti-apoptotic proteins such as c-IAP1/c-IAP2. DHEA also caused a significant decrease of TGF-β1-induced collagen production and fibroblast to myofibroblast differentiation, and inhibited PDGF-induced fibroblast migration.These findings demonstrate a disproportionate decrease of DHEA/DHEA-S in IPF patients and indicate that this molecule has multiple antifibrotic properties.