Long noncoding RNAs (lncRNAs) have been discovered to be playing important role in various biological processes. However, the contribution of lncRNAs to pulmonary artery hypertension (PAH) remains largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Here, we investigated the biological role of lncRNAs in PAH. Differences in the lncRNAs and mRNAs between hypoxia PAH rats and normoxia rats were screened using microarray analysis. The results showed that 36 lncRNAs and 519 mRNAs were upregulated in the pulmonary arteries (PAs) of hypoxia PAH rats, whereas 111 lncRNAs and 246 mRNAs were downregulated. Expressions of the screened lncRNAs, including TCONS_00034812, were validated by real-time PCR. We revealed that the expression of TCONS_00034812 was significantly downregulated in PAs of PAH rats and hypoxia pulmonary artery smooth muscle cells (PASMCs). TCONS_00034812 knockdown promoted proliferation and inhibited apoptosis of PASMCs in vitro. Moreover, TCONS_00034812 regulated PASMCs function in vitro. We found that TCONS_00034812 increased the expression of transcription factors Stox1. TCONS_00034812 and Stox1 knockdown mediated PASMCs function through MAPK signaling. Our findings imply lncRNA as a critical regulator in PAH and demonstrate the potential of gene therapy and drug development for treating PAH. The present study reveals a novel mechano responsive lncRNA-TCONS_00034812, which modulates PASMCs proliferation and apoptosis, and participates in vascular remodeling during PAH.
Keywords: TCONS_00034812; long non-coding RNAs; pulmonary arterial hypertension; pulmonary artery smooth muscle cells.
© 2017 Wiley Periodicals, Inc.