IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration.
IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration.
复制标题
IL-1 beta 在椎间盘退变过程中通过 NF-kappa B p65 途径增加髓核细胞中阿孢菌素的表达
DOI：
10.1038/s41598-017-04384-3
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发表时间：
2017-06-23
影响因子：
4.6
通讯作者：
Tian J
中科院分区：
文献类型：
--
作者：
Wang S;Liu C;Sun Z;Yan P;Liang H;Huang K;Li C;Tian J
椎间盘退变（DD）是一个多方面的慢性过程，它改变了椎间盘的结构和功能。退变的病理生理尚不完全清楚，但共识是椎间盘中编码细胞外基质（ECM）蛋白的基因的变化是导致DD的主要因素。阿司匹林是一种ECM蛋白，已被证明在退变的椎间盘中增加，但对于阿司匹林在DD中是如何调节的知之甚少。我们证实，阿霉素在患者退行性髓核中大量增加。兔椎间盘退变（IDD）模型也证实了asporin表达随退变的增加。从机制上讲，IL-1β通过激活人髓核细胞的p65通路上调阿霉素的表达。此外，p65通过结合到- 41/ - 31 bp的抑菌子介导了抑菌素的表达。在功能上，阿霉素是il -1β抑制聚集蛋白和胶原Π表达的中介，在TGF-β诱导的人髓核细胞聚集蛋白和胶原Π形成中起负向作用。因此，确定阿司匹林是聚集蛋白和胶原蛋白Π的负调节因子，并阐明其在人髓核细胞中的诱导机制，为研究阿司匹林在IDD中的诱导作用提供了新的思路。
Disc degeneration (DD) is a multifaceted chronic process that alters the structure and function of intervertebral discs. The pathophysiology of degeneration is not completely understood, but the consensus is that changes in genes encoding extracellular matrix (ECM) proteins in the disc are the leading factors contributing to DD. Asporin is an ECM protein that has been shown to be increased in degenerated intervertebral discs, but little is known about how asporin is regulated during DD. In exploring the intricate mechanism, we confirmed that asporin was abundantly increased in patients’ degenerated nucleus pulposus. Consistently, the increased asporin expression with degeneration was also proved by rabbit intervertebral disc degeneration (IDD) model. Mechanistically, IL-1β upregulated asporin expression by activating the p65 pathway in human nucleus pulposus cells. Furthermore, p65 mediated asporin expression by binding to −41/−31 bp on asporin promoter. Functionally, asporin was the intermediator of IL-1β-inhibited aggrecan and collagen Π expression and played a negative role in TGF-β-induced aggrecan and collagen Π formation in human nucleus pulposus cells. Therefore, identifying asporin as a negative regulator of aggrecan and collagen Π and elucidating its induction mechanisms in human nucleus pulposus cells provides new insight for asporin induction during IDD.