Background/Aims: We evaluated the role of serum-derived hyaluronan-associated protein (SHAP) in inflammatory bowel disease (IBD) pathogenesis and its potential as a novel IBD biomarker. Methods: We studied the SHAP expression in a mouse model of colitis and in human intestinal samples of IBD and compared serum concentrations with normal controls. Results: SHAP was expressed in the connective tissue derived from inflamed regions of the intestine. In mice, serum levels of SHAP-hyaluronic acid (SHAP-HA) were positively correlated with the histological damage of the colon (r = 0.566, p < 0.001). Serum concentration of SHAP-HA complex was significantly higher in patients with active ulcerative colitis than in those in remission, and this value was positively correlated with the erythrocyte sedimentation rate, serum level of tumor necrosis factor (TNF)-α, and endoscopic damage (r = 0.568, p < 0.001; r = 0.521, p < 0.001, and r = 0.641, p < 0.001). In patients with Crohn's disease, the serum SHAP-HA level correlated only with TNF-α (r = 0.630, p = 0.002). Conclusion: SHAP is a novel IBD biomarker that is related to disease activity in certain types of colitis, and it may affect disease pathogenesis. Future studies are needed to evaluate the therapeutic potential of this complex.

1.
Abraham C, Cho JH: Inflammatory bowel disease. N Engl J Med 2009;361:2066-2078.
[PubMed]
2.
Wang C, Tammi M, Guo H, Tammi R: Hyaluronan distribution in the normal epithelium of esophagus, stomach, and colon and their cancers. Am J Pathol 1996;148:1861-1869.
[PubMed]
3.
Genasetti A, Vigetti D, Viola M, Karousou E, Moretto P, Rizzi M, Bartolini B, Clerici M, Pallotti F, De Luca G, Passi A: Hyaluronan and human endothelial cell behavior. Connect Tissue Res 2008;49:120-123.
[PubMed]
4.
Litwiniuk M, Krejner A, Speyrer MS, Gauto AR, Grzela T: Hyaluronic acid in inflammation and tissue regeneration. Wounds 2016;28:78-88.
[PubMed]
5.
Wilkinson TS, Potter-Perigo S, Tsoi C, Altman LC, Wight TN: Pro- and anti-inflammatory factors cooperate to control hyaluronan synthesis in lung fibroblasts. Am J Respir Cell Mol Biol 2004;31:92-99.
[PubMed]
6.
Yoneda M, Suzuki S, Kimata K: Hyaluronic acid associated with the surfaces of cultured fibroblasts is linked to a serum-derived 85-kDa protein. J Biol Chem 1990;265:5247-5257.
[PubMed]
7.
Huang L, Yoneda M, Kimata K: A serum-derived hyaluronan-associated protein (SHAP) is the heavy chain of the inter alpha-trypsin inhibitor. J Biol Chem 1993;268:26725-26730.
[PubMed]
8.
Zhao M, Yoneda M, Ohashi Y, Kurono S, Iwata H, Ohnuki Y, Kimata K: Evidence for the covalent binding of SHAP, heavy chains of inter-alpha-trypsin inhibitor, to hyaluronan. J Biol Chem 1995;270:26657-26663.
[PubMed]
9.
de la Motte CA, Hascall VC, Drazba J, Bandyopadhyay SK, Strong SA: Mononuclear leukocytes bind to specific hyaluronan structures on colon mucosal smooth muscle cells treated with polyinosinic acid:polycytidylic acid: inter-alpha-trypsin inhibitor is crucial to structure and function. Am J Pathol 2003;163:121-133.
[PubMed]
10.
Kida D, Yoneda M, Miyaura S, Ishimaru T, Yoshida Y, Ito T, Ishiguro N, Iwata H, Kimata K: The SHAP-HA complex in sera from patients with rheumatoid arthritis and osteoarthritis. J Rheumatol 1999;26:1230-1238.
[PubMed]
11.
Dieleman LA, Pena AS, Meuwissen SG, van Rees EP: Role of animal models for the pathogenesis and treatment of inflammatory bowel disease. Scand J Gastroenterol Suppl 1997;223:99-104.
[PubMed]
12.
Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP: Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 1998;114:385-391.
[PubMed]
13.
Zhuo L, Kanamori A, Kannagi R, Itano N, Wu J, Hamaguchi M, Ishiguro N, Kimata K: SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. J Biol Chem 2006;281:20303-20314.
[PubMed]
14.
Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho GT, Satsangi J, Bloom S; IBD Section of the British Society of Gastroenterology: Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571-607.
[PubMed]
15.
Schreiber S, Rosenstiel P, Hampe J, Nikolaus S, Groessner B, Schottelius A, Kuhbacher T, Hamling J, Folsch UR, Seegert D: Activation of signal transducer and activator of transcription (STAT) 1 in human chronic inflammatory bowel disease. Gut 2002;51:379-385.
[PubMed]
16.
Bandyopadhyay SK, de la Motte CA, Kessler SP, Hascall VC, Hill DR, Strong SA: Hyaluronan-mediated leukocyte adhesion and dextran sulfate sodium-induced colitis are attenuated in the absence of signal transducer and activator of transcription 1. Am J Pathol 2008;173:1361-1368.
[PubMed]
17.
Kessler S, Rho H, West G, Fiocchi C, Drazba J, de la Motte C: Hyaluronan (HA) deposition precedes and promotes leukocyte recruitment in intestinal inflammation. Clin Transl Sci 2008;1:57-61.
[PubMed]
18.
Sandborn WJ, Colombel JF, Enns R, Feagan BG, Hanauer SB, Lawrance IC, Panaccione R, Sanders M, Schreiber S, Targan S, van Deventer S, Goldblum R, Despain D, Hogge GS, Rutgeerts P; International Efficacy of Natalizumab as Active Crohn's Therapy (ENACT-1) Trial Group; Evaluation of Natalizumab as Continuous Therapy (ENACT-2) Trial Group: Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med 2005;353:1912-1925.
[PubMed]
19.
Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, Sands BE, Hanauer SB, Targan S, Rutgeerts P, Ghosh S, de Villiers WJ, Panaccione R, Greenberg G, Schreiber S, Lichtiger S, Feagan BG; CERTIFI Study Group: Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N Engl J Med 2012;367:1519-1528.
[PubMed]
20.
Parikh A, Leach T, Wyant T, Scholz C, Sankoh S, Mould DR, Ponich T, Fox I, Feagan BG: Vedolizumab for the treatment of active ulcerative colitis: a randomized controlled phase 2 dose-ranging study. Inflamm Bowel Dis 2012;18:1470-1479.
[PubMed]
21.
van Rheenen PF, Van de Vijver E, Fidler V: Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 2010;341:c3369.
[PubMed]
22.
Lin WC, Wong JM, Tung CC, Lin CP, Chou JW, Wang HY, Shieh MJ, Chang CH, Liu HH, Wei SC; Taiwan Society of Inflammatory Bowel Disease Multicenter Study: Fecal calprotectin correlated with endoscopic remission for Asian inflammatory bowel disease patients. World J Gastroenterol 2015;21:13566-13573.
[PubMed]
23.
Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I: Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000;119:15-22.
[PubMed]
24.
Roseth AG, Fagerhol MK, Aadland E, Schjonsby H: Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 1992;27:793-798.
[PubMed]
You do not currently have access to this content.