Page 60 - F. Cell biology

[F. Cell biology-36]

Colocalization with MMP-7 in the distal colon is crucial for

syndecan-2 shedding during chronic inflammation

Heejeong Hong¹, Hyun-Kuk Song¹, Bohee Jang¹, Eun-Hye Park¹, Dong-Soo Han², Seong-Eun Kim³,

Eok-Soo Oh¹˙*

¹Department of Life Sciences and the Research Center for Cellular Homeostasis , Ewha Womans University, Seoul
03760, Republic of Korea, ²Department of Internal Medicine, Hanyang University College of Medicine, Guri 1923,

Republic of Korea, ³Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul 07985,

Republic of Korea

Cell surface proteoglycan, syndecan-2, was elevated during both chronic inflammation and cancer development,
and extracellular domain release of syndecan-2 was observed in cancer patients. Here, we investigated whether

inflammation triggers syndecan-2 shedding. In DSS-induced colitis mices, elevation of the shed syndecan-2 level
correlated with the increased expression of syndecan-2 and MMP-7 in distal colon tissues, and colocalization in this

colon region was a critical factor in stimulating syndecan-2 shedding. The serum levels of only IL-6 was altered in
trans-distal colon tissues: its mRNA expression level gradually increased from -9 to week-15. IL-6 directly induced

syndecan-2, MMP-7 expression and syndecan-2 shedding in ex vivo cultured distal colon tissues and cell lines.
Interestingly, hypoxic conditions increased syndecan-2 expression but attenuated syndecan-2 shedding by

suppressing MMP-7 expression. Finally, we observed that the frequency of syndecan-2 and MMP-7 colocalization
was increased in the AOM-DSS-induced mouse model of adenoma and that this colocalization was paralleled by

increased serum levels of shed syndecan-2. Together, these data demonstrate that IL-6 produced during chronic
inflammation induces syndecan-2 shedding in the distal colon by regulating MMP7