High Smad7 in the early post-operative recurrence of Crohn's disease.

High Smad7 in the early post-operative recurrence of Crohn's disease.
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DOI:
10.1186/s12967-020-02558-8
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发表时间:
2020-10-19
影响因子:
7.4
通讯作者:
Monteleone G
Monteleone G
中科院分区:
医学2区
文献类型:
--
作者:
Zorzi F;Calabrese E;Di Fusco D;De Cristofaro E;Biancone L;Casella S;Palmieri G;Monteleone G

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在人类主要炎症性肠病 (IBD) 之一的克罗恩病 (CD) 中,Smad7 过度表达,Smad7 是抑制性细胞因子 TGF-β1 的细胞内抑制剂。本研究的目的是评估 Smad7 过度表达是否发生在 CD 的早期和/或晚期。粘膜样本取自接受回结肠切除术、有或没有(早期 CD)术后内镜复发的 CD 患者的新末端回肠,以及患有长期疾病且接受肠切除术(晚期 CD)的 CD 患者的末端回肠。通过免疫组织化学检查 Smad7,并通过流式细胞术分析细胞因子表达。在内镜损伤出现之前,回肠新末端粘膜的上皮区和固有层区均含有大量表达 Smad7 的细胞。从这一阶段到内镜复发的过渡以大量 Smad7 阳性细胞的持续存在为标志,这些细胞在疾病晚期显着减少,但 Smad7 表达仍然高于正常对照。在早期病变样本中,Smad7 表达与干扰素 γ 分泌细胞的数量呈正相关。 Smad7 诱导是 CD 炎症序列中的早期事件,因此表明 Smad7 的敲除有助于预防术后复发。
In Crohn’s disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD. Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry. Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-γ-secreting cells. Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.
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