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

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.

Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway

“…distribution of TNC in the human body is an intriguing topic of study. TNC is expressed at very low levels in adult tissues compared with that in embryos, although it is expressed most abundantly in stem cells, sites of inflammation or tissue trauma, and solid tumors in adults (Uenishi et al 2014;Ning et al 2019;Zhao et al 2017;Leppanen et al 2019). Based on its role in regulating cell adhesion by binding with fibronectin and in tissue regeneration, an increasing number of basic and clinical scientists have turned their attention to the potential value of TNC in oncology (Giuffrida et al 2004;Sundquist et al 2017).…”

Novel Human Tenascin-C Function-Blocking Camel Single Domain Nanobodies

“…Next, we investigated whether Nb3 and Nb4 recognized hTNC in FFPA tissues. Therefore, we stained human colon tissue from an ulcerative colitis (UC) patient and noticed a staining pattern that resembled published TNC expression in this tissue (65)(66)(67), (Supplementary Figure 3A). We also stained tissue from human tongue tumors (OSCC) with Nb3 and Nb4 and with a commercial rabbit polyclonal anti-TNC antibody on an adjacent section, and observed similar staining patterns for TNC reminiscent of tumor matrix tracks (TMT) that have previously been described [ Figure 3A, (22)].…”

Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression

“…A genome-wide association study of African Americans found that single-nucleotide polymorphisms within the TNC gene are associated with IBD risk[ 100 ]. Ning et al [ 101 ] reported that TNC is highly expressed in the inflamed stromal area of the intestinal mucosa of IBD patients[ 101 ]. They also showed particularly high levels of serum TNC in patients with severe IBD compared with those with mild or moderate IBD[ 101 ].…”

“…Ning et al [ 101 ] reported that TNC is highly expressed in the inflamed stromal area of the intestinal mucosa of IBD patients[ 101 ]. They also showed particularly high levels of serum TNC in patients with severe IBD compared with those with mild or moderate IBD[ 101 ]. Riedl et al [ 96 ] determined that the serum levels of TNC are correlated with clinical and histological parameters of disease activity in IBD patients[ 96 ].…”