PT  - JOURNAL ARTICLE
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
TI  - Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis
AID  - 10.1183/09031936.00027412
DP  - 2013 Nov 01
TA  - European Respiratory Journal
PG  - 1309--1321
VI  - 42
IP  - 5
4099  - http://erj.ersjournals.com/content/42/5/1309.short
4100  - http://erj.ersjournals.com/content/42/5/1309.full
SO  - Eur Respir J2013 Nov 01; 42
AB  - 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