Resistance to endoplasmic reticulum stress is an acquired cellular characteristic of rheumatoid synovial cells.
Resistance to endoplasmic reticulum stress is an acquired cellular characteristic of rheumatoid synovial cells.
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DOI：
10.3892/ijmm.18.1.113
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发表时间：
2006-07
影响因子：
5.4
通讯作者：
S. Yamasaki;N. Yagishita;K. Tsuchimochi;Y. Kato;Takeshi Sasaki;T. Amano;M. Beppu;H. Aoki;Hiroshi Nakamura;K. Nishioka;T. Nakajima
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文献类型：
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作者：
S. Yamasaki;N. Yagishita;K. Tsuchimochi;Y. Kato;Takeshi Sasaki;T. Amano;M. Beppu;H. Aoki;Hiroshi Nakamura;K. Nishioka;T. Nakajima
滑膜蛋白是一种内质网（ER）驻留的E3泛素连接酶，在ER相关降解（ERAD）中起关键作用。我们发现滑膜蛋白是类风湿性关节炎（RA）的一种新的致病因子，尤其是在疾病中增殖的滑膜细胞中上调。我们试图研究滑膜素在内质网应激诱导的滑膜细胞凋亡和增殖中的作用。RA滑膜细胞（RSC）与HEK 293或HeLa细胞相比，ER应激诱导的凋亡是难治的。与骨关节炎患者的滑膜细胞相比，RSC对凋亡的抵抗力也更强。通过siRNA下调Synoviolin增加了RSC对ER应激诱导的凋亡的易感性。siRNA敲低Synoviolin基因不仅能诱导RSCs凋亡，而且能抑制RSCs的体外增殖。这些数据表明，RSC是非常难对付的ER应激诱导的凋亡，我们称之为这种特殊的属性'hyper-ERAD'。由于滑膜蛋白在RSC中过表达，并且已知作为E3泛素连接酶在ERAD系统中发挥关键作用，因此超ERAD可能存在于这些细胞中。随后，hyper-ERAD可能通过其在RA中的抗凋亡作用引起滑膜增生。进一步的分析是必要的，以解决这一点，然而，抵抗ER应激诱导的细胞凋亡，或hyper-ERAD是一个值得注意的新的细胞特征的RSC。
Synoviolin is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase which plays a critical role in ER-associated degradation (ERAD). We found that Synoviolin is a novel causative factor for rheumatoid arthritis (RA), which is especially up-regulated in proliferating synovial cells in the disease. We attempted to examine the role of Synoviolin in ER stress-induced apoptosis and proliferation of synovial cells. RA synovial cells (RSCs) were refractory to ER stress-induced apoptosis compared with HEK293 or HeLa cells. RSCs were also more resistant to the apoptosis than synovial cells from osteoarthritis patients, significantly. Down-regulation of Synoviolin by siRNA increased the susceptibility to ER stress-induced apoptosis in RSCs. Knock-down of Synoviolin by siRNA did not only induce apoptosis of RSCs but also inhibited their proliferation in vitro. These data suggest that RSCs are extraordinarily refractory to ER stress-induced apoptosis, and we termed this special property 'hyper-ERAD'. Since Synoviolin is overexpressed in RSCs, and is known to play a critical role in the ERAD system as E3 ubiquitin ligase, hyper-ERAD is likely to present in these cells. Subsequently, the hyper-ERAD may cause synovial hyperplasia through its anti-apoptotic effect in RA. Further analyses are necessary to address this point, however, resistance to ER stress-induced apoptosis, or hyper-ERAD is a noteworthy new cellular characteristic of RSCs.