Oncostatin M stimulates cell migration and proliferation by down-regulating E-cadherin in HTR8/SVneo cell line through STAT3 activation

Ko, Hyun Sun; Choi, Sae Kyung; Kang, Hee Kyung; Kim, Ho Shik; Jeon, Ji Hyun; Park, In Yang; Shin, Jong Chul

doi:10.1186/1477-7827-11-93

Cited by 20 publications

(22 citation statements)

References 32 publications

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“…Our results found that IL-27 could decrease the phosphorylation of STAT1, STAT3 and STAT5 during EMT. This is consistent with research done by Ko et al which previoulsy validated that activation of STAT3 could lead to decreased expression of E-cadherin [ 26 ]. Our results suggest that the JAK/STAT signalling pathway might be a key molecular mechanism of IL-27 activity in pulmonary fibrosis.…”

Section: Discussionsupporting

confidence: 93%

IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells

et al. 2016

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AbstractsBackgroundIL-27 is a multifunctional cytokine that has both pro-inflammatory and anti-inflammatory functions. Although IL-27 has been shown to potently inhibit lung fibrosis, the detailed mechanism of IL-27 in this process is poorly understood. Epithelial–mesenchymal transition (EMT) is one of the key mechanisms involved in pulmonary fibrosis. We assessed the effects of IL-27 on TGF-β1-induced EMT in alveolar epithelial cells.MethodsA549 cells (a human AEC cell line) were incubated with TGF-β1, IL-27, or both TGF-β1 and IL-27, and changes in E-cadherin, β-catenin, vimentin and a-SMA levels were measured using real-time PCR, western blotting and fluorescence microscopy. The related proteins in the JAK/STAT and TGF-β/Smad signalling pathways were examined by western blot.ResultsIL-27 increased the expression of epithelial phenotypic markers, including E-cadherin and β-catenin, and inhibited mesenchymal phenotypic markers, including vimentin and a-SMA in A549 cells. Moreover, TGF-β1-induced EMT was attenuated by IL-27. Furthermore, we found that TGF-β1 activated the phosphorylation of JAK1, STAT1, STAT3, STAT5, Smad1, Smad3 and Smad5, and IL-27 partially inhibited these changes in this process. When cells were treated with the STAT3 specific inhibitor wp1006 and the Smad3 specific inhibitor SIS3, the inhibition of EMT by IL-27 was significantly strengthened.ConclusionOur results suggest that IL-27 attenuates epithelial–mesenchymal transition in alveolar epithelial cells in the absence or presence of TGF-β1 through the JAK/STAT and TGF-β/Smad signalling pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-016-0084-x) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells

et al. 2016

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“…Transfection of HTR8/SVneo cells with 25 nM STAT3-specific siRNA (and not scrambled siRNA) significantly decreased the amount of STAT3 and phosphorylated STAT3, as shown in the previous study. 9 Transfection of HTR8/SVneo cells with STAT3 siRNA also significantly decreased the expression of MMP-2 and MMP-9 that was increased by OSM ( p <0.05 for both), without affecting expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein ( Fig. 1C and D ).…”

Section: Resultsmentioning

confidence: 90%

“…The activation of STAT3 by OSM was confirmed in a previous study. 9 The cells were treated with OSM (20 ng/mL) for 48 h with or without pretreatment with the STAT3 inhibitor, stattic (Tocris, R&D system, Minneapolis, MN, USA), at 0.5 µM or 1 µM for 1 h in dimethyl sulfoxide (DMSO) and subjected to Western blotting as described above.…”

Section: Methodsmentioning

confidence: 99%

STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9

Park

Choi

et al. 2016

Yonsei Med J

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PurposeOur 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 MethodsWe 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.ResultsOSM-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.ConclusionBoth 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.

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“…Recent studies demonstrated that the inhibition of STAT3 phosphorylation resulted in the suppression of proliferation, migration, invasion and increased apoptosis of HTR-8/SVneo cells 31 32 33 . Certain cytokines and other molecules enhance HTR-8/SVneo cell invasion through STAT3 phosphorylation 34 35 36 .…”

Section: Discussionmentioning

confidence: 99%

Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration

Zong

Luo

et al. 2016

Sci Rep

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In pregnancy, trophoblast proliferation, migration and invasion are important for the establishment and maintenance of a successful pregnancy. Impaired trophoblast function has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy, but the underlying mechanisms remain unclear. Indoleamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan along the kynurenine pathway, is highly expressed in the placenta and serum during pregnancy. Here, we identified a novel function of IDO in regulating trophoblast cell proliferation and migration. We showed that IDO expression and activity were decreased in unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancy. Furthermore, blocking IDO in human trophoblast cells led to reduced proliferation and migration, along with decreased STAT3 phosphorylation and MMP9 expression. Increased STAT3 phosphorylation reversed the IDO knockdown-suppressed trophoblast cell proliferation and migration. In addition, the overexpression of IDO promoted cell proliferation and migration, which could be abolished by the STAT3 signaling inhibitor (AG490). Finally, we observed similar reductions of STAT3 phosphorylation and MMP9 expression in URSA patients. These results indicate that the level of IDO expression may be associated with pregnancy-related complications, such as URSA, by affecting trophoblast cell proliferation and migration via the STAT3 signaling pathway.

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Oncostatin M stimulates cell migration and proliferation by down-regulating E-cadherin in HTR8/SVneo cell line through STAT3 activation

Cited by 20 publications

References 32 publications

IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells

IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells

STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9

Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration

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