LncRNA SOX2OT/Smad3 feedback loop promotes myocardial fibrosis in heart failure
| Autor: | Yali Ou, Chunfeng Liao, He Li, Guolong Yu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Clinical Biochemistry Biochemistry Feedback Transforming Growth Factor beta1 03 medical and health sciences Subcutaneous injection Mice 0302 clinical medicine Western blot Isoprenaline Genetics medicine Animals Smad3 Protein Molecular Biology Cell Proliferation Heart Failure Gene knockdown medicine.diagnostic_test Chemistry Cell Biology medicine.disease Fibrosis Long non-coding RNA Mice Inbred C57BL MicroRNAs 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Heart failure Cancer research Myocardial fibrosis RNA Long Noncoding Cardiomyopathies Chromatin immunoprecipitation medicine.drug |
| Zdroj: | IUBMB lifeREFERENCES. 72(11) |
| ISSN: | 1521-6551 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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