@article {Mendozaerj00274-2012, author = {Criselda Mendoza and Ana Valero Jim{\'e}nez and Claudia Rangel and Alfredo Lozano and Violeta Morales and Carina Becerril and Roberto Chavira and V{\'\i}ctor Ruiz and Lourdes Barrera and Martha Monta{\~n}o and Annie Pardo and Mois{\'e}s Selman}, title = {DHEA has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis}, elocation-id = {erj00274-2012}, year = {2012}, doi = {10.1183/09031936.00027412}, publisher = {European Respiratory Society}, abstract = {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{\textendash}29.2) versus 6.7 (2.1{\textendash}15.2) ng{\textperiodcentered}mL-1; p\<0.01; DHEA-S, median: 47 (15.0{\textendash}211) versus 85.2 (37.6{\textendash}247.0) μg{\textperiodcentered}dl-1; p\<0.001), while in females only DHEA-S was significantly decreased (median: 32.6 (15.0{\textendash}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.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/early/2012/10/25/09031936.00027412}, eprint = {https://erj.ersjournals.com/content/early/2012/10/25/09031936.00027412.full.pdf}, journal = {European Respiratory Journal} }