| 李小鹏,厉锋,董阳,等.miR-146a通过TGF-β1/SMAD通路调控脊柱结核进展的分子机制.骨科,2024,15(1): 55-62. |
| miR-146a通过TGF-β1/SMAD通路调控脊柱结核进展的分子机制 |
| Molecular Mechanism of miR-146a in Regulating the Progression of Spinal Tuberculosis via the TGF-β1/SMAD Pathway |
| 投稿时间：2023-07-27 |
| DOI：10.3969/j.issn.1674-8573.2024.01.011 |
| 中文关键词: 脊柱结核 miR-146a TGF-β1/SMAD通路 髓核细胞 |
| 英文关键词: Spinal tuberculosis miR-146a TGF-β1/SMAD pathway Nucleus pulposus cells |
| 基金项目:山东省医药卫生科技发展计划项目（202004070241）；山东省自然科学基金面上项目（ZR2020MH093）；深圳市医学三名工程项目（SZSM202111015） |
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| 中文摘要: |
| 目的 探讨miR-146a/转化生长因子-β（transforming growth factor-β1，TGF-β1）/母亲抗肢瘫（small mother against decapentaplegic，SMAD）通路在脊柱结核进展中的调控机制。方法 收集脊柱结核病人和正常病人髓核组织，验证miR-146a/TGF-β1/SMAD通路在结核髓核组织中的表达量；分离培养髓核细胞，敲低/过表达miR-146a，分别应用qPCR、Western blot、CCK-8、划痕实验验证miR-146a对TGF-β1/SMAD通路表达及髓核细胞增殖、迁移能力的影响。结果 与正常病人比较，脊柱结核病人髓核细胞增殖及迁移能力显著减低，miR-146a在脊柱结核病人髓核组织中表达量显著减低，而脊柱结核病人髓核组织中SMAD同系物2（SMAD2）、SMAD同系物3（SMAD3）、SMAD同系物4（SMAD4）、TGF-β1基因表达增高，SMAD同系物7（SMAD7）表达减低，提示miR-146a与TGF-β1/SMAD通路活性显著负相关。过表达miR-146a可抑制SMAD2、SMAD3、SMAD4、TGF-β1和促进SMAD7表达，而敲低miR-146a可促进SMAD2、SMAD3、SMAD4、TGF-β1 mRNA和抑制SMAD7表达水平。细胞实验进一步证实过表达miR-146a可促进脊柱结核病人髓核细胞增殖和迁移能力，而敲低miR-146a可显著抑制其增殖和迁移能力。结论 miR-146a是脊柱结核进展的关键调控因子，其可通过抑制TGF-β1/SMAD通路活性进而调控髓核细胞增殖及迁移活性。 |
| 英文摘要: |
| Objective To explore the regulatory mechanism of miR-146a / transforming growth factor-β1 (TGF-β1)/small mother against decapentaplegic (SMAD) signaling pathway in the progression of spinal tuberculosis. Methods The spinal tuberculosis nucleus pulposus tissues were collected and the expression of miR-146a/TGF-β1/SMAD signaling pathway in tuberculosis nucleus pulposus tissues was examined. The nucleus pulposus cells were isolated from tuberculosis nucleus pulposus tissues. Then miR-146a mimics and inhibitors were used to overexpress or knock down miR-146a. The effect of miR-146a on TGF-β1/SMAD signaling pathway was examined using qPCR and Western blotting assays. The effect of miR-146a on the proliferation and migration ability of nucleus pulposus cells were tested using CCK-8 and scratch assays. Results The proliferation and migration ability of nucleus pulposus cells in patients with lumbar tuberculosis was significantly reduced, and the expression level of miR-146a in the nucleus pulposus tissue of patients with lumbar tuberculosis patients was also significantly reduced. We also found that the expression of SMAD homologue 2 (SMAD2), SMAD3, SMAD4, and TGF-β significantly increased, and the expression of SMAD7 was reduced, indicating that the expression of miR-146a was negatively correlated to the activity of TGF-β/SMAD pathway. Furthermore, overexpression of miR-146a significantly suppressed the expression of SMAD2, SMAD3, SMAD4, TGF-β1, but suppressed the expression of SMAD7. On the contrary, knocking down miR-146a significantly promoted the expression of SMAD2, SMAD3, SMAD4, TGF-β1, but inhibited the expression of SMAD7. We also found that overexpression of miR-146a could promote the proliferation and migration ability of tuberculosis nucleus pulposus cells, but knocking down miR-146a could significantly suppress the proliferation and migration ability of tuberculosis nucleus pulposus cells. Conclusion miR-146a is one of the key regulators of spinal tuberculosis progression, which regulates the proliferation and migration activity of nucleus pulposus cells by inhibiting the TGF-β1/SMAD pathway activity. |
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