Tenascin-C Is Increased in Inflammatory Bowel Disease and Is Associated with response to Infliximab Therapy.

Longui Ning,Sha Li,Fenming Zhang,Jinghua Yu,Liang Ding,Guodong Shan,Guoqiang Xu,Chenhui Wang,Wenguo Chen,Jianguo Gao

doi:10.1155/2019/1475705

Longui Ning, Sha Li + Show 8 more

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https://doi.org/10.1155/2019/1475705

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Abstract

Tenascin-C (TNC) is an extracellular matrix glycoprotein expressed in response to inflammation and tissue damage. The role of TNC in patients with inflammatory bowel disease (IBD) is not well understood. In this study, we analyzed the expression of TNC in the inflamed mucosa of patients with ulcerative colitis (UC) and Crohn's disease (CD). Serum TNC levels were determined by the enzyme-linked immunosorbent assay (ELISA), and the levels of TNC in patients with different disease activities were compared. The expression of TNC was derived from a GEO dataset. THP-1 cells were stimulated with TNC to evaluate the proinflammatory role of TNC. We found higher TNC expression in the inflamed mucosa of patients with UC and CD compared with normal controls (NCs). TNC was mainly expressed in the stromal area of the intestinal mucosa. The median serum levels of TNC were significantly higher in UC (median 74.1 ng/ml, range 42.6–102.1 ng/ml) and CD (median 59.2 ng/ml, range 44.0–80.9 ng/ml). We also found that serum TNC levels were correlated with Mayo scores in UC and Crohn's disease activity index (CDAI) in CD. Through GSE14580, we demonstrated that patients who were nonresponsive to infliximab treatment had higher mucosal TNC mRNA expression. High TNC mRNA expression in the inflamed intestinal mucosa was associated with poor response to infliximab therapy in patients with UC. Furthermore, THP-1 cells stimulated with TNC showed increased expression of IL-6, but not TNF-α, IL-8, MCP-1, or IL-1β. Thus, increased TNC levels may participate in the pathogenesis of IBD and may serve as a biomarker for disease activity and response to treatment with infliximab.

Highlights

Inflammatory bowel disease (IBD) describes two conditions: ulcerative colitis (UC) and Crohn’s disease (CD)
A total of 131 inpatients with IBD at the First Affiliated Hospital of Zhejiang University admitted between September 2016 and December 2018 were included in the present study. ere were 40 patients with UC and 91 patients with CD. e study conformed to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee at First Affiliated Hospital of Zhejiang University. e diagnosis of UC and CD was based on World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD [19]
By using transcriptomic data from the GEO dataset, we demonstrated that high TNC expression in the inflamed intestinal mucosa was associated with poor response to infliximab therapy in patients with UC. us, mucosal TNC mRNA expression may be used as a predictor of response to infliximab

Summary

Introduction

Inflammatory bowel disease (IBD) describes two conditions: ulcerative colitis (UC) and Crohn’s disease (CD). It is a chronic intestinal disorder characterized by relapsing and remitting inflammation across the gastrointestinal tract, mainly the colon and small intestine. Previous studies have shown that tissues from IBD patients are characterized by an increase in total collagen, fibronectin, and matrix metalloproteinases (MMPs) [4,5,6], indicating collagen deposition and ECM remodeling. E roles of MMP family molecules in IBD include the regulation of epithelial barrier function, immune response, angiogenesis, fibrosis, and wound healing [7].

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