lncRNA PFAL promotes lung fibrosis through CTGF by competitively binding miR‐18a

What is it about?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease of unknown etiology with increasing morbidity and high mortality. Long non-coding RNAs (lncRNAs) are emerging as new regulatory factors in a variety of biological processes, but the role and underlying mechanisms of lncRNAs in IPF have not been explicitly delineated. Here, we show that:(1)lncRNA PFAL (pulmonary fibrosis-associated lncRNA) promoted fibrogenesis through modulation of miR-18a, whereas knockdown of PFAL attenuated TGF-β1-induced fibrogenesis in lung fibroblasts;(2) Enhanced expression of miR-18a attenuated TGF-β1-induced lung fibrogenesis by targeting regulation of CTGF, whereas knockdown of miR-18a resulted in ECM deposition and fibrosis in lung fibroblasts; (3) PFAL acted as a competing endogenous RNA (ceRNA) of miR-18a: forced expression of PFAL reduced the expression and activity of miR-18a to activate CTGF and promote fibrogenesis in lung fibroblasts;(4)Silencing PFAL alleviated BLM-induced lung fibrosis in mice. Taken together, the results of our study identified lncRNA PFAL as a new pro-fibrotic molecule that acts as a ceRNA of miR-18a during lung fibrosis and demonstrated PFAL as a novel therapeutic target for the prevention and treatment of lung fibrosis.

Featured Image