STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9.
10.3349/ymj.2016.57.3.761
- Author:
Hyun Sun KO
1
;
Byung Joon PARK
;
Sae Kyung CHOI
;
Hee Kyung KANG
;
Ahyoung KIM
;
Ho Shik KIM
;
In Yang PARK
;
Jong Chul SHIN
Author Information
1. Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea. jcshin@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Oncostatin M;
trophoblasts;
signaling pathway;
signal transducer and activator of transcription (STAT)3;
extracellular signal-regulated kinases (ERK)1/2
- MeSH:
Blotting, Western;
Cell Movement/*drug effects;
Cell Proliferation/*drug effects;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Humans;
Matrix Metalloproteinase 2/genetics/*metabolism;
Matrix Metalloproteinase 9/genetics/*metabolism;
Oncostatin M/genetics/*metabolism;
Phosphorylation/drug effects;
RNA, Messenger/metabolism;
RNA, Small Interfering;
STAT3 Transcription Factor/*metabolism;
Signal Transduction/*drug effects
- From:Yonsei Medical Journal
2016;57(3):761-768
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 mechanisms associated 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 invasion activity 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 increased invasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extent by STAT3 inhibition. CONCLUSION: Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activation of STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.
