Colocalization with MMP-7 in the Distal Colon is Crucial for Syndecan-2 Shedding in Dextran Sulfate Sodium-Induced Colitis Mice

Heejeong Hong,1 Hyun-Kuk Song,1 Bohee Jang,1 Eunhye Park,1 Dong Soo Han,2 Seong-Eun Kim,3 Eok-Soo Oh1 1Department of Life Sciences, Ewha Womans University, Seoul, South Korea; 2Department of Internal Medicine, Hanyang University College of Medicine, Guri, South Korea; 3Department of Internal Medicine, Ewha Womans University School of Medicine, Ewha Medical Research Institute, Seoul, South KoreaCorrespondence: Eok-Soo OhDepartment of Life Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemoon-Gu, Seoul, 03760, South KoreaTel +82-2-3277-3761Fax +82-2-3277-3760Email OhES@ewha.ac.krIntroduction: Syndecan-2 expression is elevated during chronic inflammation and cancer development, and its shedding is observed in cancer patients. However, it remained unknown whether inflammation triggers syndecan-2 shedding.Methods: The colitis model was produced in C57BL/6 mice by oral administration of 2– 3% dextran sulfate sodium (DSS) in the drinking water. Syndecan-2 and MMP-7 expression levels in tissues and cells were detected by real-time PCR, Western blotting, and immunohistochemistry. Shed syndecan-2 levels were detected by slot blotting. For tissue culture, colon tissues were divided into proximal, transverse, and distal parts, and incubated in culture media.Results: In C57BL/6 mice with DSS-induced colitis, syndecan-2 shedding began to increase after week 12 of chronic inflammation and continued to increase at week 15. The level of shed syndecan-2 correlated with the colocalization of syndecan-2 and MMP-7 in distal colon tissues. The mRNA expression of IL-6 was increased specifically in trans-distal colon tissues from weeks 9 to 15. IL-6 induced syndecan-2 expression and shedding and MMP-7 expression in ex vivo-cultured distal colon tissues and adenoma cell lines derived from the distal colon. IL-6 treatment induced STAT3 phosphorylation and MMP-7 expression in DLD-1 cells. The application of MMP-7 to ex vivo-cultured colon tissues increased the shedding of syndecan-2 to the culture medium.Conclusion: Our findings suggest that chronic inflammation induces syndecan-2 shedding via the site-specific colocalization of syndecan-2 with MMP-7 in the distal colon.Keywords: chronic inflammation, syndecan-2, MMP-7, shedding