Syndecan-1 (SDC1) and its endo-beta-D-glucuronidase heparanase (HPA) are implicated in the maintenance of intestinal barrier function, but their detailed functions in Crohn’s disease (CD) are not fully investigated. The aim of this study was to determine alteration patterns of SDC1 and HPA and their potential roles in evaluating disease activity and differentiating CD from intestinal tuberculosis (ITB).
Tissue and serum specimens were obtained from 89 patients, including 15 patients with functional bowel disorders, 18 active patients with ITB, and 56 patients with CD (remission = 19, active = 37). Basic clinical data were collected and routine blood tests were analyzed. SDC1 and HPA were measured by immunohistochemistry, enzyme-linked immunosorbent assay, reverse transcriptase polymerase chain reaction, and western blot. Colonic epithelial cells were incubated with recombinant HPA, tumor necrosis factor alpha (TNF-α), and mycobacterium tuberculosis culture filtrate protein to detect the alterations of SDC1 and HPA.
In the CD group, SDC1 was significantly decreased in mucosa and increased in serum, whereas HPA level in both were elevated. Such alterations were associated with clinicopathological features representing disease activity and injury severity and were not available in functional bowel disorder and ITB groups. Recombinant HPA incubation increased soluble SDC1 in culture supernatants (P = 2 × 10−4), and low-dose TNF-α effectively enhanced HPA’s activity (P = 3 × 10−6). Exogenous TNF-α destroyed cellular SDC1 and raised HPA expressions dose dependently, whereas mycobacterium tuberculosis culture filtrate protein showed no effects.
Unique alterations of SDC1 and HPA are shown in both patients with CD and in vitro model. The results indicate SDC1 and HPA are potential markers for CD in evaluating its disease activity and differentiating it from ITB.
Article first published online 18 March 2013
*Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
†Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
‡Department of Gastroenterology, 401 Hospital of Chinese PLA, Qingdao, China
§Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, China
‖Department of Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Reprints: Ye Chen, MD, PhD, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China (e-mail: email@example.com).
Supported by National Natural Science Foundation of China (YC, 81070291), Program for New Century Excellent Talents in University (YC, China, NCET-10-0091), and Medical Research Fund of Guangdong Province (XJ, A2010364).
The authors have no conflicts of interest to disclose.
Y. Chen and Y. Zhang have contributed equally to this study.
Received July 16, 2012
Accepted November 27, 2012