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연세대학교 의과대학 Yonsei Medical Journal Yonsei Medical Journal 제57권 제3호
발행연도
2016.1
수록면
761 - 768 (8page)

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Purpose: Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanismsassociated with these events in the immortalized human trophoblast cell line HTR8/SVneo. Materials and Methods: We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasionactivity were further determined via Western blot and gelatin zymography. Results: OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increasedinvasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extentby STAT3 inhibition. Conclusion: Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activationof STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.

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