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微小 RNA-129-5p 通过调节 FADD 影响椎间盘退变中髓核细胞的免疫特权和细胞凋亡。

MicroRNA-129-5p affects immune privilege and apoptosis of nucleus pulposus cells via regulating FADD in intervertebral disc degeneration.

机构信息

Department of Neonatology, The First Hospital of Jilin University, Changchun, Jilin, China.

Department of Pharmaceutical Chemistry, Jilin University School of Pharmaceutical Sciences, Changchun, Jilin, China.

出版信息

Cell Cycle. 2020 Apr;19(8):933-948. doi: 10.1080/15384101.2020.1732515. Epub 2020 Mar 11.

Abstract

Literatures indicate that microRNA-129-5p (miR-129-5p) or Fas-associated death domain (FADD) is related to intervertebral disc degeneration (IDD), but the effect of miR-129-5p/FADD axis on IDD is not studied. The study aimed to investigate whether miR-129-5p influenced immune privilege and nucleus pulposus (NP) cell apoptosis in rats with IDD via regulating FADD.A rat model with caudal IDD was established, and injected with miR-129-5p agomir or miR-129-5p antagomir to figure out the character of miR-129-5p in the cell apoptosis and inflammation in the nucleus pulposus (NP) tissues of IDD rats. NP cells were grouped as the same ways for determining proliferation, apoptosis, and senescence in NP cells of IDD rats. Annexin V-FITC/PI double staining detected the apoptosis of macrophages and CD8 cells co-cultured via transfected NP cells. Expression of miR-129-5p, FADD, collagen I, collagen II, aggrecan and Sox-9 in NP tissues and cells were determined.Up-regulated miR-129-5p decreased FADD, collagen I and elevated collagen Ⅱ, aggrecan, and Sox-9 in NP tissues and repressed inflammation in serum and NP tissues in IDD rats. Up-regulated miR-129-5p facilitated proliferation, inhibited senescence, apoptosis, and decreased FADD, collagen I and increased collagen Ⅱ, aggrecan, and Sox-9 in NP cells of IDD rats. Elevated miR-129-5p promoted the apoptosis of macrophages and CD8 cells.We pronounced that up-regulated miR-129-5p inhibited the apoptosis and facilitated the proliferation of NP cells, as well as the apoptosis of macrophages and CD8 cells via decreased FADD in IDD, suggesting that miR-129-5p had a protective effect on IDD.

摘要

文献表明 microRNA-129-5p(miR-129-5p)或 Fas 相关死亡结构域(FADD)与椎间盘退变(IDD)有关,但 miR-129-5p/FADD 轴对 IDD 的影响尚未研究。本研究旨在探讨 miR-129-5p 是否通过调节 FADD 影响免疫豁免和髓核(NP)细胞凋亡。建立了尾侧 IDD 大鼠模型,并注射 miR-129-5p 激动剂或 miR-129-5p 拮抗剂,以了解 miR-129-5p 在 IDD 大鼠 NP 组织细胞凋亡和炎症中的作用。NP 细胞也分组进行实验,以确定 IDD 大鼠 NP 细胞的增殖、凋亡和衰老。通过转染的 NP 细胞共培养,用 Annexin V-FITC/PI 双染色检测巨噬细胞和 CD8 细胞的凋亡。检测 NP 组织和细胞中 miR-129-5p、FADD、胶原 I、胶原 II、聚集蛋白聚糖和 Sox-9 的表达。上调的 miR-129-5p 降低了 NP 组织和细胞中的 FADD、胶原 I,并增加了胶原 II、聚集蛋白聚糖和 Sox-9,同时抑制了 IDD 大鼠血清和 NP 组织中的炎症。上调的 miR-129-5p 促进了 IDD 大鼠 NP 细胞的增殖,抑制了衰老、凋亡,并降低了 FADD、胶原 I,增加了胶原 II、聚集蛋白聚糖和 Sox-9。上调的 miR-129-5p 促进了巨噬细胞和 CD8 细胞的凋亡。我们发现,上调的 miR-129-5p 通过降低 FADD,抑制了 IDD 中 NP 细胞的凋亡和促进了增殖,以及巨噬细胞和 CD8 细胞的凋亡,表明 miR-129-5p 对 IDD 具有保护作用。

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