Long non‐coding RNA MFAT1 promotes skeletal muscle fibrosis by modulating the miR‐135a‐5p‐Tgfbr2/Smad4 axis as a ceRNA
| Autor: | Qingyan Chen, Jinrong Lin, Jiwu Chen, Yaying Sun, Xiaobao Yang, Zhiwen Luo, Zheci Ding, Shaohua Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine TGFβ pathway Apoptosis Endogeny Biology miR‐135a‐5p Skeletal muscle fibrosis Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Fibrosis medicine Animals long noncoding RNA Muscle Skeletal Cells Cultured Cell Proliferation Smad4 Protein skeletal muscle fibrosis Gene knockdown Competing endogenous RNA Receptor Transforming Growth Factor-beta Type II RNA Skeletal muscle Original Articles Cell Biology Prognosis medicine.disease Long non-coding RNA Cell biology Mice Inbred C57BL MicroRNAs 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Molecular Medicine RNA Long Noncoding Original Article |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.16508 |
| Popis: | Fibrosis after skeletal muscle injury is common in sports and can cause irreversible damage to the biomechanical properties of skeletal muscle. Long non‐coding RNAs (lncRNAs) have been validated to act as important modulators in the fibrosis of various organs. Here, we reported a novel lncRNA (the skeletal muscle fibrosis‐associated transcript 1, lnc‐MFAT1), which was highly expressed in skeletal muscle fibrosis. We demonstrate that lnc‐MFAT1 knockdown can reduce TGFβ‐induced fibrosis in vitro and attenuate skeletal muscle fibrosis after acute contusion in mice. Further study showed that lnc‐MFAT1 acted as a competitive endogenous RNA of miR‐135a‐5p. Besides, the miR‐135a‐5p inhibition obviously promoted TGFβ‐induced fibrosis in vitro via enhancing its target genes Tgfbr2/Smad4. Moreover, we discovered that lnc‐MFAT1 regulates Tgfbr2/Smad4 expression by sponging miR‐135a‐5p to exert competing endogenous RNA function, resulting in TGFβ pathway activation. In conclusion, our study identified a crucial role of lnc‐MFAT1‐miR‐135a‐Tgfbr2/Smad4 axis in skeletal muscle fibrosis, providing a promising treatment option against skeletal muscle fibrosis. |
| Databáze: | OpenAIRE |
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