Details

Autor(en) / Beteiligte

• Ikari, Jun
• Nelson, Amy J
• Obaid, Jannah
• Giron-Martinez, Alvaro
• Ikari, Kumiko
• Makino, Fumihiko
• Iwasawa, Shunichiro
• Gunji, Yoko
• Farid, Maha
• Wang, Xingqi
• Basma, Hesham
• Demeo, Dawn
• Feghali-Bostwick, Carol
• Holz, Olaf
• Rabe, Klaus
• Liu, Xiangde
• Rennard, Stephen I
• Mari, Bernard

Titel

Reduced microRNA-503 expression augments lung fibroblast VEGF production in chronic obstructive pulmonary disease

Ist Teil von

• PloS one, 2017-09, Vol.12 (9), p.e0184039-e0184039

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis. In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release. Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined. The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD. Primary adult lung fibroblasts were isolated from patients with or without COPD. MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without inflammatory cytokines, IL-1β and tumor necrosis factor (TNF)-α. MiR-503 expression was decreased in COPD lung fibroblasts. The expression of miR-503 was positively correlated with %FVC, %FEV1, and %DLco as well as IL-6, -8, PGE2, HGF, KGF, and VEGF in the absence or presence of IL-1ß/TNF-α. In addition, IL-8 and VEGF release from COPD lung fibroblasts were increased compared to those from control. Exogenous miR-503 inhibited VEGF release from primary adult and fetal lung fibroblasts but not IL-8 release. As expected, COPD fibroblasts proliferated more slowly than control fibroblasts. MiR-503 did not affect proliferation of either control or COPD lung fibroblasts. MiR-503 inhibition of VEGF protein production and mRNA was mediated by direct binding to the 3' untranslated region of VEGF mRNA. Endogenous miR-503 was differently regulated by exogenous stimulants associated with COPD pathogenesis, including IL-1ß/TNF-α, TGF-ß1 and PGE2. Endogenous miR-503 inhibition augmented VEGF release by IL-1ß/TNF-α and TGF-ß1 but not by PGE2, demonstrating selectivity of miR-503 regulation of VEGF. In conclusions, reduced miR-503 augments VEGF release from lung fibroblasts from patients with COPD. Since VEGF contributes to disturbed vasculature in COPD, altered miR-503 production might play a role in modulating fibroblast-mediated vascular homeostasis in COPD.