Expression profiles of endoplasmic reticulum stress-related molecules in demyelinating lesions and multiple sclerosis
Expression profiles of endoplasmic reticulum stress-related molecules in demyelinating lesions and multiple sclerosis
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DOI：
10.1177/1352458511399114
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发表时间：
2011-07-01
影响因子：
5.8
通讯作者：
FitzGerald, Una
中科院分区：
文献类型：
--
作者：
Cunnea, Paula;Mhaille, Aoife Ni;FitzGerald, Una
背景资料：越来越多的证据表明内质网（ER）应激信号通路是多发性硬化（MS）的潜在治疗靶点。目的：建立ER应激标志物在人死后MS组织脱髓鞘活检标本和显微解剖病变中的表达谱。免疫组化检测C/EBP同源蛋白（CHOP）、免疫球蛋白重链结合蛋白（BiP）、和缺氧标志物抗原D-110的活检从三个原发或继发进展型MS患者，三个临床孤立综合征患者，和一个病灶性癫痫患者进行。激光捕获显微切割正常，perilesion和病变组织从死后MS组织和非患病的对照组织进行，然后通过实时PCR检测ER应力genes.Results：在活检标本中，ER和缺氧应激分子的表达增加的范围内的细胞类型在大多数的主动脱髓鞘病变和perilesions检测。实时PCR分析表明，相对于对照白色物质，在正常外观的白色物质中ER应激基因的表达在统计学上显著升高。此外，CHOP在活动斑块周围的表达显著增加（p < 0.01）。结论：我们的结果显示，ER应激分子在病变组织中的表达升高，为进一步研究ER应激信号通路作为治疗MS的潜在治疗靶点提供了令人信服的证据。
Background: Increasing evidence associates the endoplasmic reticulum (ER) stress signalling pathway as a potential treatment target in multiple sclerosis (MS).Objective: To establish the expression profile of markers of ER stress both in demyelinating biopsy specimens and microdissected lesions in human post-mortem MS tissue.Methods: Immunohistochemical detection of C/EBP homologous protein (CHOP), immunoglobulin heavy chain binding protein (BiP), and hypoxia marker antigen D-110 in biopsies from three patients with MS primary or secondary progressive, three patients with clinically isolated syndrome, and one patient with lesional epilepsy was carried out. Laser capture microdissection of normal, perilesion and lesion tissue from post-mortem MS tissue and non-diseased control tissue was performed, followed by real-time PCR to detect ER stress genes.Results: In biopsy specimens, increased expression of the ER and hypoxic stress molecules in a range of cell types in most of the actively demyelinating lesions and perilesions was detected. Real-time PCR analysis demonstrated statistically significant elevated expression of the ER stress genes in normal-appearing white matter relative to control white matter. Moreover, significantly increased expression of CHOP was detected in the perilesion of active plaques (p < 0.01).Conclusions: Our results, showing detection of elevated expression of ER stress molecules in lesional tissue, offer compelling evidence for further investigation of the ER stress signalling pathway as a potential therapeutic target for the treatment of MS.