Stricturing Crohn’s disease (CD) is characterised by transmural intestinal fibrosis accompanied with creeping fat (CrF) formation.1 Such pathological features were successfully recapitulated in a mouse model for the first time by Xiong et al 2 who performed repeated endoscopy-guided forceps biopsies on mouse colon. This method, although effective, requires specific training to use small animal endoscopes and accessories, which are not readily available in many labs. Here, we developed a simpler, reliable and repeatable method to generate mouse transmural fibrosis and CrF using a high-frequency electrocautery device and an (often secondhand) endoscopic submucosal dissection knife, both of which are readily available in tertiary endoscopy centres. We then characterised the model via histological staining and transcriptome sequencing and explored the intersection of differentially expressed genes (DEGs) between mouse CrF and publicly accessible human CrF datasets.3 Additionally, we investigated the impact of dexamethasone (DEX) on mouse colon fibrosis and CrF formation. Histopathological analyses demonstrated that increased inflammatory cell infiltration and abnormal extracellular matrix (ECM) deposition were common features of CrF in CD patients (figure 1A–F).4 5 Our model was generated by inserting a Dual knife (Olympus, Tokyo) into mouse distal colon (4 cm from the anus) and applying controlled electrical cautery (cutting mode, voltage set to 5 V) to the mucosa (figure 1G–H). After four cycles of cautery injuries, we observed enlargement of the mesenteric fat and evidence of fat wrapping around the injured area of the colon (figure 1I). Repeated colonic cautery induced transmural and penetrating fibrosis into the wrapping fat with smaller and more numerous adipocytes, including increased inflammatory cell infiltration (figure 1J–L), similar to what is observed in CD patients. We further identified DEGs between the model CrF and the control group mesenteric adipose tissue through transcriptome sequencing. The volcano plot revealed 2443 DEGs (1308 upregulated …

中文翻译：

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用于研究狭窄性克罗恩病中透壁肠纤维化和蠕行脂肪形成的新型小鼠模型


狭窄性克罗恩病 （CD） 的特征是透壁肠纤维化伴有匍匐脂肪 （CrF） 形成。Xiong 等人 2 首次在小鼠模型中成功概括了这种病理特征，他们对小鼠结肠进行了重复的内窥镜引导下镊子活检。这种方法虽然有效，但需要专门培训才能使用小动物内窥镜和附件，而许多实验室并不容易获得这些设备。在这里，我们开发了一种更简单、可靠且可重复的方法，使用高频电烙装置和（通常是二手的）内窥镜粘膜下解剖刀来生成小鼠透壁纤维化和 CrF，这两种方法在三级内窥镜检查中心都很容易获得。然后，我们通过组织学染色和转录组测序对模型进行了表征，并探索了小鼠 CrF 和公开可访问的人类 CrF 数据集之间差异表达基因 （DEG） 的交集。此外，我们还研究了地塞米松 （DEX） 对小鼠结肠纤维化和 CrF 形成的影响。组织病理学分析表明，炎症细胞浸润增加和异常细胞外基质 （ECM） 沉积是 CD 患者 CrF 的常见特征（图 1A-F）.4 5 我们的模型是通过将双刀（奥林巴斯，东京）插入小鼠远端结肠（距肛门 4 cm）并施加受控电灼（切割模式，电压设置为 5 V）来生成的粘膜（图 1G-H）。经过四个周期的烧灼损伤后，我们观察到肠系膜脂肪增大，并且有证据表明脂肪包裹在结肠受伤区域周围（图 1I）。 重复的结肠烧灼诱导透壁和穿透纤维化进入包裹脂肪，脂肪细胞更小、数量更多，包括炎症细胞浸润增加（图 1J-L），类似于在 CD 患者中观察到的情况。我们通过转录组测序进一步鉴定了模型 CrF 和对照组肠系膜脂肪组织之间的 DEGs。火山图显示 2443 个 DEGs（1308 个上调......