Involvement of endoplasmic reticulum stress in inflammatory bowel disease: a different implication for colonic and ileal disease?
Involvement of endoplasmic reticulum stress in inflammatory bowel disease: a different implication for colonic and ileal disease?
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DOI：
10.1371/journal.pone.0025589
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Laukens D
中科院分区：
文献类型：
--
作者：
Bogaert S;De Vos M;Olievier K;Peeters H;Elewaut D;Lambrecht B;Pouliot P;Laukens D
内质网（ER）应激已被认为在炎症性肠病（IBD）中发挥作用。未折叠蛋白反应（UPR）的三个分支（ATF 6，IRE 1和PERK）具有不同的作用，不一定同时激活。在23名对照、15名溃疡性结肠炎（UC）和54名克罗恩病（CD）患者的结肠和回肠活检中研究了UPR相关基因的表达。在5名对照、UC和CD患者的结肠和回肠样品中在蛋白质水平证实了这种表达。在结肠IBD中，HSPA 5、PDIA 4和XBP 1在mRNA和/或蛋白水平上显著增加，表明ATF 6和IRE 1分支的激活。结肠IBD与EIF 2A磷酸化增加相关，提示PERK分支活化，但未观察到随后的GADD 34诱导。在回肠CD中，未观察到UPR相关基因的差异表达，但我们的数据表明对照组回肠粘膜中UPR的基础活化较高。这通过16种UPR相关基因的表达增加得到证实，因为其中12种基因在回肠对照中的表达显著高于结肠对照。衣霉素刺激健康个体的结肠和回肠样品显示，尽管回肠粘膜表现出这种更高的基础UPR活化，但它仍然对ER应激有反应，甚至比结肠粘膜更有反应。在结肠IBD相关炎症中观察到三个UPR相关臂的激活。然而，尽管EIF 2A激活，发炎的结肠组织并没有增加GADD 34的表达，这通常涉及ER稳态的重建。这项研究还表明，在健康的回肠粘膜中存在组成性UPR激活，在炎症过程中没有进一步的激活。因此，UPR的参与在结肠和回肠之间是不同的，这可能是回肠或结肠疾病发展的一个因素。
Endoplasmic reticulum (ER) stress has been suggested to play a role in inflammatory bowel disease (IBD). The three branches (ATF6, IRE1 and PERK) of the unfolded protein response (UPR) have different roles and are not necessarily activated simultaneously. Expression of UPR-related genes was investigated in colonic and ileal biopsies of 23 controls, 15 ulcerative colitis (UC) and 54 Crohn's disease (CD) patients. This expression was confirmed at protein level in colonic and ileal samples of five controls, UC and CD patients. HSPA5, PDIA4 and XBP1s were significantly increased in colonic IBD at mRNA and/or protein levels, indicating activation of the ATF6 and IRE1 branch. Colonic IBD was associated with increased phosphorylation of EIF2A suggesting the activation of the PERK branch, but subsequent induction of GADD34 was not observed. In ileal CD, no differential expression of the UPR-related genes was observed, but our data suggested a higher basal activation of the UPR in the ileal mucosa of controls. This was confirmed by the increased expression of 16 UPR-related genes as 12 of them were significantly more expressed in ileal controls compared to colonic controls. Tunicamycin stimulation of colonic and ileal samples of healthy individuals revealed that although the ileal mucosa is exhibiting this higher basal UPR activation, it is still responsive to ER stress, even more than colonic mucosa. Activation of the three UPR-related arms is seen in colonic IBD-associated inflammation. However, despite EIF2A activation, inflamed colonic tissue did not increase GADD34 expression, which is usually involved in re-establishment of ER homeostasis. This study also implies the presence of a constitutive UPR activation in healthy ileal mucosa, with no further activation during inflammation. Therefore, engagement of the UPR differs between colon and ileum and this could be a factor in the development of ileal or colonic disease.
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影响因子：
6.3
作者：
Ishiguro, Y
通讯作者：
Ishiguro, Y
影响因子：
15.8
作者：
Heazlewood CK;Cook MC;Eri R;Price GR;Tauro SB;Taupin D;Thornton DJ;Png CW;Crockford TL;Cornall RJ;Adams R;Kato M;Nelms KA;Hong NA;Florin TH;Goodnow CC;McGuckin MA
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McGuckin MA
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
11.8
作者：
Shen, JS;Chen, X;Prywes, R
通讯作者：
Prywes, R
影响因子：
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作者：
Satsangi, J.;Silverberg, M. S.;Colombel, J-F
通讯作者：
Colombel, J-F