Zorzi Francesca, Calabrese Emma, Di Fusco Davide, De Cristofaro Elena, Biancone Livia, Casella Sara, Palmieri Giampiero, Monteleone Giovanni
Department of Systems Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Roma, Italy.
Department of Biomedicine and Prevention, Anatomic Pathology Unit, University of Rome "Tor Vergata", Roma, Italy.
J Transl Med. 2020 Oct 19;18(1):395. doi: 10.1186/s12967-020-02558-8.
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.
在人类主要的炎症性肠病（IBD）之一的克罗恩病（CD）中，细胞内抑制性细胞因子TGF-β1的抑制剂Smad7存在过表达。本研究的目的是评估Smad7过表达是否发生在CD的早期和/或晚期。
从接受回结肠切除术的CD患者的新末端回肠获取黏膜样本，这些患者有或没有（早期CD）术后内镜复发，以及从接受肠切除术的患有长期疾病的CD患者的末端回肠获取样本（晚期CD）。通过免疫组织化学检测Smad7，并通过流式细胞术分析细胞因子表达。
在内镜病变出现之前，新末端回肠的黏膜在上皮和固有层中均含有大量表达Smad7的细胞。从这个阶段到内镜复发的转变以大量Smad7阳性细胞的持续存在为标志，在疾病后期这些细胞数量显著减少，然而，Smad7表达仍高于正常对照。在有早期病变的样本中，Smad7表达与分泌干扰素-γ的细胞数量呈正相关。
Smad7的诱导是CD中炎症序列的早期事件，因此表明敲低Smad7有助于预防术后复发。
