Long noncoding RNA TUG1 promotes cardiac fibroblast transformation to myofibroblasts via miR‑29c in chronic hypoxia.

Cardiac fibroblast‑myofibroblast transformation (FMT) contributes to the fibrotic deterioration evoked by chronic hypoxia. Growing evidence implicates long noncoding RNAs (lncRNAs) in various types of cardiac physiological and pathological processes, especially in cardiac fibrosis. In the present study, the lncRNA Taurine Upregulated Gene 1 (TUG1), reported as a regulator of hypoxia fibrosis in the lungs, was found to also be an important regulator of cardiac FMT. Specifically, the possible role of TUG1 in cardiac FMT and fibrosis under chronic hypoxia was investigated. It was revealed that the degree of fibrosis in heart tissues collected from congenital heart surgery patients with low pulse oxygen saturation and mice housed under chronic hypoxic and atmospheric pressure conditions was negatively correlated with pulse oxygen saturation. Moreover, TUG1 expression was positively correlated with the degree of fibrosis but negatively correlated with pulse oxygen saturation. Cardiac fibroblasts showed increased myofibroblast marker, collagen I and α‑SMA expression levels as the hypoxia time increased. TUG1 knockdown ameliorated the hypoxia‑induced FMT. A bioinformatics analysis predicted that TUG1 had miR‑29c binding sites in its 3'‑UTR and miR‑29c is a key regulator of cardiac fibrosis. The present study demonstrated that TUG1, along with miR‑29c, may contribute to cardiac FMT activation and promote fibrosis in chronic hypoxia.