LncRNA SOX2OT/Smad3 feedback loop promotes myocardial fibrosis in heart failure.
Long noncoding RNA SOX2OT is associated with myocardial fibrosis (MF) in heart failure (HF). This article aims to investigate the role of SOX2OT in MF. We constructed HF mouse models by subcutaneous injection of isoprenaline (ISO). Cardiac fibroblasts (CFs) were treated with ISO to induce MF.Hematoxylin-eosin, Masson, and Sirius-red staining were used to identify myocardial injury and collagen deposition in heart tissues. The relationship among SOX2OT, miR-138-5p, TGF-β1, and Smad3 were evaluated by chromatin immunoprecipitation and luciferase reporter assay. The gene and protein expression were verified by quantitative real-time PCR and western blot. We found that SOX2OT was up-regulated in HF mice and ISO-induced CFs. SOX2OT knockdown reduced myocardial injury and collagen deposition in HF mice. The expression of collagen I, α-SMA, TGF-β1, and p-Smad3 were inhibited by SOX2OT down-regulation in HF mice and ISO-induced CFs. Furthermore, TGF-β1 was a target gene of miR-138-5p and indirectly regulated by SOX2OT. SOX2OT promoted MF in HF by activating TGF-β1/Smad3, and then Smad3 interacted with the SOX2OT promoter and formed a positive feedback loop. In conclusion, our work verifies that SOX2OT/Smad3 feedback loop promotes MF in HF. Thus, SOX2OT is potentially a novel therapeutic target for MF in HF.
['Ou|Yali|Y|0000-0001-6226-5512', 'Liao|Chunfeng|C|', 'Li|He|H|', 'Yu|Guolong|G|']
D000818:Animals D009202:Cardiomyopathies D049109:Cell Proliferation D005246:Feedback D005355:Fibrosis D005786:Gene Expression Regulation D006333:Heart Failure D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D035683:MicroRNAs D062085:RNA, Long Noncoding D051900:Smad3 Protein D053773:Transforming Growth Factor beta1
SOX2OT feedback loop myocardial fibrosis heart failure TGF-β1/Smad3