Ozanne James, Shek Brandon, Stephen Louise A, Novak Amanda, Milne Elspeth, Mclachlan Gerry, Midwood Kim S, Farquharson Colin
The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
Royal (Dick) School of Veterinary Studies, University of Edinburgh, United Kingdom.
Matrix Biol Plus. 2022 May 23;14:100112. doi: 10.1016/j.mbplus.2022.100112. eCollection 2022 Jun.
Inflammatory Bowel Disease (IBD) is a grouping of chronic inflammatory disorders of the gut. Tenascin-C is a pro-inflammatory, extracellular matrix protein found upregulated in IBD patients and whilst a pathological driver of chronic inflammation, its precise role in the etiology of IBD is unknown. To study tenascin-C's role in colitis pathology we investigated its expression in a murine model of IBD. Wild-type (WT) or tenascin-C knockout (KO) male mice were left untreated or treated with dextran sodium sulphate (DSS) in their drinking water. Tenascin-C was upregulated at the mRNA level in the colitic distal colon of day eight DSS treated mice, coinciding with significant increases in gross and histological pathology. Immunohistochemistry localized this increase in tenascin-C to areas of inflammation and ulceration in the mucosa. Tenascin-C KO mice exhibited reduced gross pathology in comparison. These differences also extended to the histopathological level where reduced colonic inflammation and tissue damage were found in KO compared to WT mice. Furthermore, the severity of the distal colon lesions were less in the KO mice after 17 days of recovery from DSS treatment. This study demonstrates a role for tenascin-C as a driver of inflammatory pathology in a murine model of IBD and thus suggests neutralizing its pro-inflammatory activity could be explored as a therapeutic strategy for treating IBD.
炎症性肠病（IBD）是一组肠道慢性炎症性疾病。腱生蛋白-C是一种促炎性细胞外基质蛋白，在IBD患者中上调，虽然它是慢性炎症的病理驱动因素，但其在IBD病因学中的具体作用尚不清楚。为了研究腱生蛋白-C在结肠炎病理中的作用，我们在IBD小鼠模型中研究了其表达。野生型（WT）或腱生蛋白-C基因敲除（KO）雄性小鼠不进行处理或通过在饮用水中添加葡聚糖硫酸钠（DSS）进行处理。在DSS处理8天的小鼠的结肠远端，腱生蛋白-C在mRNA水平上上调，同时肉眼和组织病理学病变显著增加。免疫组织化学显示，腱生蛋白-C的这种增加定位于黏膜炎症和溃疡区域。相比之下，腱生蛋白-C基因敲除小鼠的肉眼病变减轻。这些差异也延伸到组织病理学水平，与野生型小鼠相比基因敲除小鼠的结肠炎症和组织损伤减轻。此外，在从DSS处理中恢复17天后，基因敲除小鼠远端结肠病变的严重程度较低。这项研究证明了腱生蛋白-C在IBD小鼠模型中作为炎症病理驱动因素的作用，因此表明中和其促炎活性可作为治疗IBD的一种治疗策略进行探索。
