Klausen Pia, Karstensen John Gásdal, Coskun Mehmet, Săftoiu Adrian, Vilmann Peter, Cowland Jack Bernard, Riis Lene Buhl
Gastro Unit, Copenhagen University Hospital Herlev and Gentofte, DK-2730 Herlev, Denmark.
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark.
Gastroenterol Res Pract. 2018 May 24;2018:9307848. doi: 10.1155/2018/9307848. eCollection 2018.
Small mothers against decapentaplegic (SMAD)4 and SMAD7 are key regulatory components in the immunosuppressive transforming growth factor- (TGF-) signaling pathway, which is defective in inflammatory bowel disease (IBD). SMAD4 may play an important role in the pathogenesis of IBD as indicated in experimental models of colitis.
To examine the ileal expression levels of SMAD4 and to correlate these with CD disease activity.
The material comprised 29 CD patients (13 with active disease, 16 in remission) and 9 asymptomatic patients referred for ileocolonoscopy as part of an adenoma surveillance program serving as controls. Patients were examined with ileocolonoscopy. Corresponding ileal biopsies were obtained for histological analysis and assessment of SMAD4 and SMAD7 protein expression by immunohistochemistry (IHC).
The protein expression of SMAD4 was significantly downregulated in ileal tissue sections from CD patients as compared to healthy controls ( < 0.001). Further, luminal SMAD4 expression was inversely correlated with endoscopic ( = -0.315; = 0.05) and histopathological activity ( = -0.40; = 0.013).
The SMAD4 epithelial protein level was markedly downregulated in CD patients and inversely correlated with disease activity. This may contribute to defective mucosal TGF- signaling in active IBD.
小母亲抗脱靶蛋白4（SMAD）4和SMAD7是免疫抑制性转化生长因子-（TGF-）信号通路中的关键调节成分，该信号通路在炎症性肠病（IBD）中存在缺陷。如在结肠炎实验模型中所示，SMAD4可能在IBD的发病机制中起重要作用。
检测SMAD4在回肠中的表达水平，并将其与克罗恩病（CD）的疾病活动度相关联。
研究材料包括29例CD患者（13例疾病活动期，16例缓解期）和9例无症状患者，这些无症状患者因腺瘤监测计划接受回结肠镜检查作为对照。对患者进行回结肠镜检查。获取相应的回肠活检组织用于组织学分析，并通过免疫组织化学（IHC）评估SMAD4和SMAD7蛋白表达。
与健康对照相比，CD患者回肠组织切片中SMAD4的蛋白表达明显下调（<0.001）。此外，肠腔SMAD4表达与内镜检查（=-0.315；=0.05）和组织病理学活动度（=-0.40；=0.013）呈负相关。
CD患者中SMAD4上皮蛋白水平明显下调，且与疾病活动度呈负相关。这可能导致活动期IBD中黏膜TGF-信号通路缺陷。
