Colocalization with mmp-7 in the distal colon is crucial for syndecan-2 shedding in dextran sulfate sodium-induced colitis miceopen access
- Authors
- Hong, Heejeong; Song, Hyun-Kuk; Jang, Bohee; Park, Eunhye; Han, Dong Soo; Kim, Seong-Eun; Oh, Eok-Soo
- Issue Date
- Sep-2021
- Publisher
- Dove Medical Press Ltd
- Keywords
- chronic inflammation; syndecan-2; MMP-7; shedding
- Citation
- Journal of Inflammation Research, v.14, pp.4987 - 5000
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Inflammation Research
- Volume
- 14
- Start Page
- 4987
- End Page
- 5000
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/140965
- DOI
- 10.2147/JIR.S329234
- Abstract
- Introduction: 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.
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