Novel lncRNA LNC_000113 Drives the Activation of Pulmonary Adventitial Fibroblasts through Modulating PTEN/Akt/FoxO1 Pathway

Abstract

The activation of pulmonary adventitial fibroblasts (PAFs) is one of the key components of pulmonary arterial remodelling in pulmonary arterial hypertension (PAH). Emerging evidence indicates that lncRNAs may play fibrotic roles in a range of diseases. In this present study, we identified a novel lncRNA, LNC_000113, in pulmonary adventitial fibroblasts (PAFs) and characterised its role in the Galectin-3-induced activation of PAFs in rats. Galectin-3 led to elevated expression of lncRNA LNC_000113 in PAFs. The expression of this lncRNA was primarily PAF enriched. A progressive increase in lncRNA LNC_000113 expression was observed in rats with monocrotaline (MCT)-induced PAH rats. Knockdown of lncRNA LNC_000113 cancelled the Galectin-3′s fibroproliferative effect on PAFs and prevented the transition of fibroblasts to myofibroblasts. The loss-of-function study demonstrated that lncRNA LNC_000113 activated PAFs through the PTEN/Akt/FoxO1 pathway. These results propose lncRNA LNC_000113 drives the activation of PAFs and promotes fibroblast phenotypic alterations.