Pathway Map Details
Immune response_Oncostatin M signaling via JAK-Stat in human cells
Object list (links open in MetaCore):
Oncostatin M signaling via JAK-Stat in human cells
Oncostatin M is a multifunctional cytokine produced by activated T lymphocytes, monocytes, microglia. It is structurally and functionally related to the subfamily of hematopoietic and neurotrophic cytokines known as the Interleukin 6 (IL6)-type cytokine family .
Human Oncostatin M and mouse Oncostatin M signaling pathways are different. Human Oncostatin M signaling is mediated by its binding to two receptor complexes: the type I OSM receptor complex ( LIF receptor ) consisting of Interleukin 6 signal transducer ( gp130 ) and Leukemia inhibitory factor receptor subunits ( LIFR ), and the type II OSM receptor complex ( OSM receptor ) consisting of gp130 and OSM receptor beta ( OSMR ) subunits. Mouse Oncostatin M uses only one receptor complex: OSM receptor, but not LIF receptor .
Binding of Oncostatin M to its receptor subunits induces the Janus kinases (JAK)/ signal transducer and activator of transcription (STAT) signaling pathway. Janus kinase 1 ( Jak1), Janus kinase 2 ( Jak2) and Tyrosine kinase 2 ( Tyk2 ) may associate with OSM receptor and LIF receptor , , . Signaling capacity of LIFR or OSMR depends on the cellular context. Activated JAKs recruit and activate STAT proteins. Phosphorylated STATs then dimerize, translocate to the nucleus, bind to regulatory elements in the promoter of OSM-responsive genes and induce gene expression. Oncostatin M predominantly activates Signal transducers and activators of transcription 1, 3 and 5 ( STAT1, STAT3 and STAT5 ) in a variety of cell types .
Suppressor of cytokine signaling 3 ( SOCS-3 ) is an inhibitor of Oncostatin M signals. SOCS-3 transcription may be stimulated by Oncostatin M .
Oncostatin M is involved in a variety of biological activities such as inflammation, remodeling of extracellular matrix and modulation of cell growth and differentiation and other .
Oncostatin M may regulate cell growth, e.g., via Vascular endothelial growth factor A ( VEGF-A ) or Cyclin D1. Oncostatin M induces VEGF promoter activity in an OSM receptor/ STAT-3 -dependent manner . Oncostatin M regulates Cyclin D1 expression via STAT3 in a cell specific -dependent manner. It is shown, that Oncostatin M inhibits expression of Cyclin D1 in fetal hepatocytes but up-regulates in hepatic tumor cells .
Oncostatin M regulates inflammation both directly and indirectly via the production of other cytokines and their receptors. For example, Oncostatin M may activate transcription of inflammatory reactant Serpin peptidase inhibitor clade A member 3 ( SERPINA3 (ACT) ) via STAT1 and/or STAT3 . In addition, Oncostatin M induces transcription of eosinophil-specific C-C chemokine that is implicated in the pathogenesis of eosinophilic inflammatory diseases - Chemokine ligand 11 ( Eotaxin ). This process is STAT3 -dependent .
Remodeling of the extracellular matrix is important for healing the damaged tissue induced by inflammatory responses. Oncostatin M stimulation of the JAK/ STAT signaling pathway in primary chondrocytes leads to induction of important element regulation of this process - e.g., Matrix metallopeptidase 1 ( MMP1 ) and TIMP metallopeptidase inhibitor 1 ( TIMP-1) , .
Oncostatin M participates in induction of epithelial-to-mesenchymal transition (EMT) of renal cells via JAK/ STAT1 and STAT2. STAT activation leads to E-cadherin downregulation and alpha-smooth muscle actin upregulation . Normally, EMT seems to be a process, induced during wound healing after injury. And EMT can be a normal recovery process in renal cells, because proliferating myofibroblasts are produced during it. EMT of renal cells can lead to renal fibrosis progression , , . , .
- Tanaka M, Miyajima A
Oncostatin M, a multifunctional cytokine. Reviews of physiology, biochemistry and pharmacology. 2003;149:39-52
- Chen SH, Benveniste EN
Oncostatin M: a pleiotropic cytokine in the central nervous system. Cytokine & growth factor reviews 2004 Oct;15(5):379-91
- Levy JB, Schindler C, Raz R, Levy DE, Baron R, Horowitz MC
Activation of the JAK-STAT signal transduction pathway by oncostatin-M cultured human and mouse osteoblastic cells. Endocrinology 1996 Apr;137(4):1159-65
- Hermanns HM, Radtke S, Haan C, Schmitz-Van de Leur H, Tavernier J, Heinrich PC, Behrmann I
Contributions of leukemia inhibitory factor receptor and oncostatin M receptor to signal transduction in heterodimeric complexes with glycoprotein 130. Journal of immunology (Baltimore, Md. : 1950) 1999 Dec 15;163(12):6651-8
- Halfter H, Postert C, Friedrich M, Ringelstein EB, Stogbauer F
Activation of the Jak-Stat- and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells. Brain research. Molecular brain research. 2000 Sep 15;80(2):198-206
- Magrangeas F, Boisteau O, Denis S, Jacques Y, Minvielle S
Negative regulation of onconstatin M signaling by suppressor of cytokine signaling (SOCS-3). European cytokine network 2001 Apr-Jun;12(2):309-15
- Repovic P, Fears CY, Gladson CL, Benveniste EN
Oncostatin-M induction of vascular endothelial growth factor expression in astroglioma cells. Oncogene 2003 Nov 6;22(50):8117-24
- Matsui T, Kinoshita T, Hirano T, Yokota T, Miyajima A
STAT3 down-regulates the expression of cyclin D during liver development. The Journal of biological chemistry 2002 Sep 27;277(39):36167-73
- Kordula T, Rydel RE, Brigham EF, Horn F, Heinrich PC, Travis J
Oncostatin M and the interleukin-6 and soluble interleukin-6 receptor complex regulate alpha1-antichymotrypsin expression in human cortical astrocytes. The Journal of biological chemistry 1998 Feb 13;273(7):4112-8
- Faffe DS, Flynt L, Mellema M, Moore PE, Silverman ES, Subramaniam V, Jones MR, Mizgerd JP, Whitehead T, Imrich A, Panettieri RA Jr, Shore SA
Oncostatin M causes eotaxin-1 release from airway smooth muscle: synergy with IL-4 and IL-13. The Journal of allergy and clinical immunology 2005 Mar;115(3):514-20
- Korzus E, Nagase H, Rydell R, Travis J
The mitogen-activated protein kinase and JAK-STAT signaling pathways are required for an oncostatin M-responsive element-mediated activation of matrix metalloproteinase 1 gene expression. The Journal of biological chemistry 1997 Jan 10;272(2):1188-96
- Nightingale J, Patel S, Suzuki N, Buxton R, Takagi KI, Suzuki J, Sumi Y, Imaizumi A, Mason RM, Zhang Z
Oncostatin M, a cytokine released by activated mononuclear cells, induces epithelial cell-myofibroblast transdifferentiation via Jak/Stat pathway activation. Journal of the American Society of Nephrology : JASN 2004 Jan;15(1):21-32
- Sun DF, Fujigaki Y, Fujimoto T, Yonemura K, Hishida A
Possible involvement of myofibroblasts in cellular recovery of uranyl acetate-induced acute renal failure in rats. The American journal of pathology 2000 Oct;157(4):1321-35
- Strutz F, Muller GA
Transdifferentiation comes of age. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2000 Nov;15(11):1729-31
- Poulsom R, Alison MR, Cook T, Jeffery R, Ryan E, Forbes SJ, Hunt T, Wyles S, Wright NA
Bone marrow stem cells contribute to healing of the kidney. Journal of the American Society of Nephrology : JASN 2003 Jun;14 Suppl 1:S48-54
- Li MX, Liu BC
Epithelial to mesenchymal transition in the progression of tubulointerstitial fibrosis. Chinese medical journal 2007 Nov 5;120(21):1925-30