IndraLab

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OSM activates OSMR. 45 / 46
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"Notably, Osmrb transcripts were increased in VmSC5s by OSM, suggestive of a feed-forward loop."
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"In mice, oncostatin M receptor (OSMR) and leukemia inhibitory factor receptor (LIFR) are selectively activated by the respective cognate ligands while OSM activates both the OSMR and LIFR in humans, which prevents efficient translation of mouse data into potential clinical applications."
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"Indeed, OSM reduced neurosphere cell proliferation and increased p-STAT3, OSMR and GFAP."
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"For example, ERK1/2, PI3K, and STAT1/3 can be activated by OSM binding the LIFR or OSMR, but only signaling through the OSMR can activate STAT5, p38, JNK, and possibly PKC-δ and STAT622.OSM has been identified as a potential therapeutic target for treatment of inflammatory diseases."
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"Furthermore, OSM upregulated OSMR-specific mRNA in human VSMCs."
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"Additionally, OSM induced biological effects by activating functional receptor complexes of the common signal transducing component gp130 and OSMRβ or LIFR, which are mainly involved in chronic inflammatory and cardiovascular diseases, cancer and rheumatoid arthritis ."
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"Together, these findings suggest a potential model of bidirectional myeloid cell-astrocyte crosstalk in which (1) Gal-9 produced by astrocytes upregulates Osm via Dectin-1 in myeloid cells and (2) myeloid cell-derived Osm triggers beneficial OsmR signaling in astrocytes."
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"OSM can activate OSMR- or LIFR-containing receptor complexes to engage downstream signaling."
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"The mRNA levels of both OSMR and HGF showed a gradual increase when MSCs were treated with increasing concentrations of OSM from 0.5 to 5 ng/ml (XREF_FIG, XREF_FIG)."
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"LIFR and gp130 can be activated by either LIF or OSM, but OSMR and gp130 is activated only by OSM [18]."
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"gp130 and OSMR is activated only by OSM, but gp130 and LIFR can be activated by either LIF, OSM or both."
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"LIFR:gp130-expressing cells proliferated with LIF, and OSM, while OSM also induced the proliferation of OSMR:gp130-expressing cells."
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"In the ileum of newly diagnosed patients with CD, the same observations were made with increased mucosal OSM (FC = 17.9, P = 6.4E-04) and borderline increased OSMR (FC = 1.4, P = 5.2E-02) as compared with the ileum of control patients without IBD (Figs."
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"OSM can activate OSMR- or LIFR-containing receptor complexes to engage downstream signaling."
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"Induction of IL-4R and OSMR in NEC by OSM stimulation."
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"In this study we have clearly demonstrated that OSM induction of IL-6, RANKL, OSMR, gp130 and IL-1R1 in mouse SFs requires expression of its ligand specific receptor, OSMR."
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"For this purpose, human GBM cell lines LN18 and LN229 showing basal levels of OSMR (XREF_SUPPLEMENTARY B) were treated with OSM (50 ng/ml) for 12 hours and tested for a panel of markers."
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"OSM can signal though both the LIFR (OSMR type I in humans) and OSMR (OSMR type II in humans) in humans and rats, while in mice, only signaling via the OSMR is possible."
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"OSM also upregulates SOCS3 (a STAT3 target gene) and additional mesenchymal markers, including VIM (encodes Vimentin), CDH2 (encodes N-cadherin), OSMR (encodes OSM receptor subunit β; OSMRβ), STAT3, and the EMT-TFs SNAI1 (encodes Snail), TWIST1, ZEB1, and ZEB2 (Fig. 1h)."
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"The drug 423F is a gp130 modulator that acts via promoting gp130 homodimerization and preventing IL-6 and Oncostatin M-induced heterodimerization with IL-6R and OSMR respectively."
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"Because OSM is required to trigger the interaction of OSMR with EGFR in astrocytes that do not express oncogenic EGFRvIII, we assessed the influence of OSM on EGFR and STAT3 signaling in these cells."
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"OSMR was reported to form a heterodimerized receptor with glycoprotein 130 and could be activated specifically by its ligand OSM."
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"To investigate whether B14 and B21 monoclonal antibodies (mAbs) inhibit OSM-induced dimerization of OSMR with IL6ST, we immunoprecipitated OSMR-IL6ST heterodimer complex cross-linked after treating with anti-OSMR antibody or control IgG."
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"TME-derived oncostatin M (OSM) was shown to mediate tumor progression and CSC expansion by activating its receptor, OSMR (26)."
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"By contrast, OSM treatment stimulated robust interaction of OSMR with EGFR in the control astrocytes (XREF_FIG)."
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"Mechanistically, OSM activates the heterodimeric receptor complex gp130:OSMR [ xref ], resulting in the activation of JAK/STAT [ xref ] and MAPK signaling pathways."
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"In an in vitro model, IL-6 family cytokine oncostatin-M (OSM) induces cancer cell EMT and escape from the targeted drug-induced apoptosis in an OSM receptor (OSMR)/JAK1/STAT3-dependent manner [58]."
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"Moreover, JAK inhibition prevented OSM induction of OSMR feed-forward loop signaling (Fig. 5B)."
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"On the molecular level this usage of OSM from different species results in the stimulation of different receptor complexes : human OSM exclusively binds to the type I gp130 and LIFR system in mouse cells; murine OSM, however, exclusively activates the type II gp130 and OSMR system."
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"Herein, a chromatin immunoprecipitation (ChIP) assay was performed after the cells were stimulated with the ligand OSM that activates OSMR signaling in the presence or absence of STAT3 inhibitor of phosphorylation and promoter binding activity, named S3I-201 inhibitor and found that OSM stimulation enhanced the binding of STAT3 transcription factor on the promoters of ITGAV, ITGB3, and ITGB8 genes, which was abrogated when the cells were treated with S3I-201 (Fig. 4d, e and Supplementary Fig. 5a)."
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"In non-tumor cells, EGFR-OSMR can be activated synergistically by the ligands EGF and OSM [ xref ]."
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"OSM activates both OSMR and LIFR in humans, while mice osm (mOSM) is generally capable of osmr binding only."
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"Moreover, OSMR is induced by OSM ligand, suggesting that a positive feedback loop is engaged to promote greater OSMR/JAK/STAT3 activation and maintain the induced mesenchymal and CSC cell state."
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"gp130 and LIFR can be activated by LIF or OSM, but gp130 and OSMR is activated by OSM only."
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"Importantly, OSM induces the dimerization of OSMR with another receptor partner IL6ST."
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"OSM also activates the STAT pathway via Y917 and Y945 of OSMRβ and activates the Shc-ERK-MAPK pathway via Y861 ( Hermanns, 2015 )."
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"Examining these 37 genes in Osmr Mx1-Cre HSCs stimulated with OSM (Supplemental Table 3) revealed several patterns; (I) 17 genes were no longer induced by OSM in Osmr Mx1-Cre HSCs, (II) 6 genes were induced by OSM in both control Mx1-Cre and Osmr Mx1-Cre HSCs, and (III) 10 genes were induced by OSM in control Mx1-Cre HSCs but repressed by OSM in Osmr Mx1-Cre HSCs."
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"When coupled with the observation that OSM and OSMR are significantly elevated in PDAC, and OSMR is induced by OSM, the unique signaling emanating from the OSMR justifies a more thorough analysis of OSM and the signaling cascades described here."
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"Focusing on genes induced by OSM signaling in control Mx1-Cre HSCs, we found that only some of these genes are no longer induced by OSM signaling in Osmr Mx1-Cre HSCs."
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"Taken together, OSM-neutralizing therapies for peripheral immune-mediated diseases have not been successful so far, which may underscore the complex nature of this molecule and the importance of identifying the optimal therapeutic window.First, in humans, OSM can signal via the OSMR (consisting of gp130 and OSMRβ) and leukemia inhibitory factor (LIF)R (consisting of gp130 and LIFRβ), which implies that LIFR signaling might be activated when OSM is used as a drug."
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"In a mouse model, OSMR overexpressing SCC cells treated with OSM showed significant increases in lung colonisation."
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"Thus, YAP and TEAD1 upregulate OSM in CMs, and OSM upregulates YAP and TEAD1, as well as OSMR through YAP and TEAD1, in CMs, suggesting that YAP, TEAD1, and OSM and OSMR form an amplification loop to enhance OSM function and promote de-differentiation of CMs."
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"Supported by LUMINEX-ELISA and RNA-Seq analyses of PCCs, PSCs, and MØ isolated from PSC–PCC and PSC–MØ–PCC co-cultures, they found that MØ-derived Oncostatin M (OSM) activated the OSM receptor (OSMR) on PSCs and stimulated expression of inflammation-related secreted ligands, which in turn induced a protumor environment to activate proliferative and migratory signaling pathways in PCCs, implying therapeutic potential by targeting the MØs–PSC–PCC interaction through OSM–OSMR complex."
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"In addition, HSCs with reduction or loss of OSMRβ appear to incur compensatory activation of OSM-stimulated genes indicating a more complex, tissue-dependent regulation of OSM-OSMRβ signaling than was previously understood.Future studies will be necessary to understand the mechanisms underlying tissue-dependent differences in Osmr transcript abundance and OSMRβ protein abundance in the B6;129-Osmr /J model."
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"The perpetuation of this effect involves a feed-forward loop, where OSM stimulates transcriptional upregulation of the OSM receptor (OSMR), thus reinforcing the mesenchymal phenotype and stemness characteristics in PDAC cells (Polak et al., 2023)."
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