Progranulin derived engineered protein Atsttrin suppresses TNF-α-mediated inflammation in intervertebral disc degenerative disease.
Progranulin derived engineered protein Atsttrin suppresses TNF-α-mediated inflammation in intervertebral disc degenerative disease.
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颗粒体蛋白前体衍生的工程蛋白 Atsttrin 抑制椎间盘退行性疾病中 TNF-α 介导的炎症
DOI：
10.18632/oncotarget.22766
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发表时间：
2017-12-12
期刊：
影响因子：
--
通讯作者：
Cheng L
中科院分区：
文献类型：
--
作者：
Ding H;Wei J;Zhao Y;Liu Y;Liu L;Cheng L
Atsttrin是一种由颗粒蛋白前体（PGRN）的三个片段组成的工程分子，具有相当的抗炎能力。椎间盘退变（IDD）与炎症有关，其中TNF-α起关键作用。本研究旨在探讨Atsttrin在椎间盘退变中的作用及其机制。本研究以小鼠和人椎间盘为材料，采用免疫组化法检测了TNF-α在椎间盘组织中的表达，并采用ELISA法检测了外周血清中TNF-α的水平。取小鼠IVD进行番红O和HE染色。对原代培养的人髓核细胞进行免疫组化、荧光染色、Western Blot、ELISA和RT-PCR检测。本研究发现IDD患者椎间盘和外周血中TNF-α表达增高。有趣的是，Atsttrin通过离体研究有效地抑制TNF-α介导的小鼠椎间盘中的catalysis。在原代人椎间盘中，Atsttrin存在时，TNF-α诱导的炎性细胞因子显著减少。机制研究表明Atsttrin通过抑制TNF-α诱导的炎症反应而保护椎间盘退变。这些发现表明Atsttrin是椎间盘退行性疾病的潜在分子靶点。
Atsttrin, an engineered molecule composed of three fragments of progranulin (PGRN), exerts comparable anti-inflammation ability. Intervertebral disc degeneration (IDD) is involved in inflammation in which TNF-α plays a key role. This study aims to examine the effect and the mechanism of Atsttrin in the pathogenesis of intervertebral disc degeneration. For this purpose, we took advantage of murine and human intervertebral disc (IVD) and examined the expression of TNF-α in IVD tissues using immunohistochemistry and TNF-α level in peripheral sera by ELISA assay. Moreover, murine IVD was taken to undergo the Safranin O and HE staining. Furthermore, primary human nucleus pulposus cells were used for immunohistochemistry staining, fluorescent staining, Western Blot, ELISA assay and RT-PCR assay. Herein we found TNF-α expression was elevated in intervertebral disc and peripheral sera in patients with IDD. Interestingly, Atsttrin effectively inhibited TNF-α-mediated catabolism in murine disc by ex vivo study. TNF-α-induced inflammatory cytokines were strongly reduced in presence of Atsttrin in primary human disc. Mechanism study indicated Atsttrin protected against intervertebral disc degeneration by inhibiting TNF-α-induced inflammation. These findings show that Atsttrin is a potential molecular target for disc degenerative diseases.
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影响因子：
5.6
作者：
Kim, Jae-Sung;Ellman, Michael B.;Yan, Dongyao;An, Howard S.;Ranjan, K. C.;Li, Xin;Chen, Di;Xiao, Guozhi;Cs-Szabo, Gabriella;Hoskin, David W.;Buechter, Doug D.;Van Wijnen, Andre J.;Im, Hee-Jeong
通讯作者：
Im, Hee-Jeong
DOI：
10.1016/j.bbrc.2013.02.034
发表时间：
2013-03-29
影响因子：
3.1
作者：
Purmessur, D.;Walter, B. A.;Roughley, P. J.;Laudier, D. M.;Hecht, A. C.;Iatridis, James
通讯作者：
Iatridis, James
促生蛋白：一种生长因子，一种新型的TNFR配体和药物靶标。
影响因子：
13.5
作者：
Liu, Chuan-ju;Bosch, Xavier
通讯作者：
Bosch, Xavier
影响因子：
3.5
作者：
Liu CJ
通讯作者：
Liu CJ
影响因子：
27.4
作者：
Dudek M;Yang N;Ruckshanthi JP;Williams J;Borysiewicz E;Wang P;Adamson A;Li J;Bateman JF;White MR;Boot-Handford RP;Hoyland JA;Meng QJ
通讯作者：
Meng QJ