Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF-α and Smad Signaling Pathway.
Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF-α and Smad Signaling Pathway.
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αFollistatin-Like 1 Attenuation 通过与 TNF 和 Smad 信号通路相互作用抑制小鼠椎间盘退变。
DOI：
10.1155/2021/6640751
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发表时间：
2021
影响因子：
--
通讯作者：
Cheng L
中科院分区：
文献类型：
--
作者：
Wang S;Wei J;Shi J;He Q;Zhou X;Gao X;Cheng L
炎症在椎间盘退变（IDD）中起着重要作用。卵泡抑素样蛋白1（FSTL 1）在多种炎性疾病中起促炎作用。 本研究的目的是研究是否可以通过抑制FSTL-1的表达来延缓IDD。 我们在野生型和FSTL-1+/-小鼠中建立了穿刺诱导的IDD模型，并收集了小鼠的椎间盘（IVD）。采用番红O染色观察IVD组织的软骨缺损情况，HE染色观察IVD组织的形态学变化。采用免疫组化、实时荧光定量PCR和免疫印迹法检测FSTL-1和相关炎症指标在IVD组织中的表达。 在增龄性IDD模型中，FSTL-1的表达水平随着IDD程度的加重而升高。在穿刺诱导的IDD模型中，FSTL-1敲除小鼠与野生型小鼠相比表现出退化程度降低。进一步的实验表明，FSTL-1敲低还显著降低了IVD中相关炎症因子的水平。体外实验表明，FSTL-1敲低显著降低TNF-α诱导的炎症。具体而言，炎症因子考克斯-2、iNOS、MMP-13和ADAMTS-5的表达水平降低。FSTL-1的敲低通过抑制P-Smad 1/5/8、P-Erk 1/2和P-P65的表达来减轻炎症。 FSTL-1的敲低通过抑制TNF-α反应和Smad通路活性来减轻炎症，并最终延迟IDD。
Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases. The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression. We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting. In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF-α-induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65. Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF-α response and Smad pathway activity and ultimately delayed IDD.
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影响因子：
3.5
作者：
Gu SX;Li X;Hamilton JL;Chee A;Kc R;Chen D;An HS;Kim JS;Oh CD;Ma YZ;van Wijnen AJ;Im HJ
通讯作者：
Im HJ
影响因子：
--
作者：
Fischer R;Maier O
通讯作者：
Maier O
影响因子：
4.6
作者：
Fan N;Sun H;Wang Y;Wang Y;Zhang L;Xia Z;Peng L;Hou Y;Shen W;Liu R;Yin J;Peng Y
通讯作者：
Peng Y
阻断卵泡抑素样 1 可减轻博莱霉素诱导的小鼠肺纤维化
DOI：
10.1084/jem.20121878
发表时间：
2015-02-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dong Y;Geng Y;Li L;Li X;Yan X;Fang Y;Li X;Dong S;Liu X;Li X;Yang X;Zheng X;Xie T;Liang J;Dai H;Liu X;Yin Z;Noble PW;Jiang D;Ning W
通讯作者：
Ning W
miR-194-5p 的炎症依赖性下调通过靶向 CUL4A 和 CUL4B 导致人椎间盘退变
影响因子：
5.6
作者：
Chen, Zhi;Han, Yingchao;Qian, Lie
通讯作者：
Qian, Lie