TY - JOUR T1 - DHEA has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00027412 SP - erj00274-2012 AU - Criselda Mendoza AU - Ana Valero Jiménez AU - Claudia Rangel AU - Alfredo Lozano AU - Violeta Morales AU - Carina Becerril AU - Roberto Chavira AU - Víctor Ruiz AU - Lourdes Barrera AU - Martha Montaño AU - Annie Pardo AU - Moisés Selman Y1 - 2012/01/01 UR - http://erj.ersjournals.com/content/early/2012/10/25/09031936.00027412.abstract N2 - 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. ER -