Colocalization with MMP-7 in the Distal Colon is Crucial for Syndecan-2 Shedding in Dextran Sulfate Sodium-Induced Colitis Mice
- 주제(키워드) chronic inflammation , syndecan-2 , MMP-7 , shedding
- 주제(기타) Immunology
- 설명문(일반) [Hong, Heejeong; Song, Hyun-Kuk; Jang, Bohee; Park, Eunhye; Oh, Eok-Soo] Ewha Womans Univ, Dept Life Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Han, Dong Soo] Hanyang Univ, Dept Internal Med, Coll Med, Guri, South Korea; [Kim, Seong-Eun] Ewha Womans Univ, Ewha Med Res Inst, Dept Internal Med, Sch Med, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 DOVE MEDICAL PRESS LTD
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183650
- 본문언어 영어
- Published As http://dx.doi.org/10.2147/JIR.S329234
- PubMed https://pubmed.ncbi.nlm.nih.gov/34616168
초록/요약
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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