TY - JOUR T1 - Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis JF - European Respiratory Journal JO - Eur Respir J SP - 1309 LP - 1321 DO - 10.1183/09031936.00027412 VL - 42 IS - 5 AU - Criselda Mendoza-Milla 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 - 2013/11/01 UR - http://erj.ersjournals.com/content/42/5/1309.abstract N2 - Idiopathic pulmonary fibrosis (IPF) is an ageing-related lung disorder characterised by expansion of the myofibroblast population and aberrant lung remodelling. 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. Plasma DHEA/DHEA-S was significantly decreased in male IPF patients (median (range) DHEA: 4.4 (0.2–29.2) versus 6.7 (2.1–15.2) ng·mL−1, p<0.01; DHEA-S: 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 (32.6 (15.0–303.0) versus 68.3 (16.4–171) μg·dL−1, p<0.001). DHEA caused a decrease in fibroblast proliferation and an approximately two-fold increase in fibroblast apoptosis, probably 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 cellular inhibitor of apoptosis (c-IAP)1 and c-IAP2. DHEA also caused a significant decrease of transforming growth factor-β1-induced collagen production and fibroblast to myofibroblast differentiation, and inhibited platelet-derived growth factor-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. DHEA/DHEA-S is abnormally decreased in IPF patients and this adrenal steroid has strong antifibrotic effects in vitro http://ow.ly/nD9sz ER -