Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn's disease

Xiao-Xian Qian; Chen-Wen Cai; Han-Yang Li; Li-Jie Lai; Dong-Juan Song; Yu-Qi Qiao; Jun Shen; Zhi-Hua Ran

doi:10.1177/1756284819880733

Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn's disease

Therap Adv Gastroenterol. 2019 Oct 16:12:1756284819880733. doi: 10.1177/1756284819880733. eCollection 2019.

Authors

Xiao-Xian Qian¹, Chen-Wen Cai², Han-Yang Li², Li-Jie Lai², Dong-Juan Song², Yu-Qi Qiao², Jun Shen³, Zhi-Hua Ran⁴

Affiliations

¹ State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, Shanghai, Shanghai, China.
² State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, Shanghai, Shanghai, China.
³ Jun Shen State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, Shanghai, 160 Pu Jian Ave, Shanghai 200127, China.
⁴ State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, Shanghai, 160 Pu Jian Ave, Shanghai 200127, China.

Abstract

Objectives: Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn's disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability.

Methods: Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively.

Results: Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI (r = 0.582, p = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all p < 0.05). Furthermore, uc.261 was positively correlated with DAI (r = 0.824, p = 0.008), HI (r = 0.672, p = 0.021), and intestinal permeability (r = 0.636, p = 0.012), while negatively correlated with body weight (r = -0.574, p = 0.035), colon length (r = -0.866, p = 0.017), and TJP expression (all p < 0.05) in colitis mice.

Conclusions: Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice.

Keywords: Crohn’s disease; T-UCR; disease activity; intestinal permeability; uc.261.