Oncostatin-M-Receptor

Oncostatin M-specific receptor subunit beta, also known as oncostatin M receptor (OSMR), is one of the receptor proteins for its ligand "oncostatin M," a cytokine that in humans is encoded by the OSMR gene.

OSMR is a member of the type I cytokine receptor family. This protein heterodimerizes with the interleukin-6 signal transducerto the type II oncostatin M receptor and with the interleukin-31 receptor A to the interleukin-31 recept or, thus transmitting oncostatin M- and interleukin-31-induced signals.

OSMR is expressed in non-hematopoietic cells, hepatocytes, mesothelial cells, glial cells, and epithelial cells in various organs and mammary glands (West NR et al (2018). The OSM receptor is expressed on endothelial and stromal/fibroblast cells in mouse lung. In vitro expression of OSMR in fetal hepatocytes is upregulated by OSM stimulation (Kamiya A et al.1999). Furthermore, OSMR expression has been shown to be induced by parathyroid hormone in osteoblasts and OSM.

Signal transduction: Intracellular signaling is initiated by extracellular binding of the ligand OSM (Oncostatin M; MIM 165095) to OSMR-gp130 complexes. These are formed by dimerization with the versch. Receptor subunits formed.

Oncostatin M: The receptor ligand oncostatin M is a member of the IL6 -cytokine family. Many IL6 cytokines use gp130 as a common receptor subunit. OSM binds to the gp130 receptor subunit and triggers phosphorylation of tyrosine residues at the intracellular receptor domain by Janus kinase 1 and 2 (JAK1/JAK2). Downstream signaling activation leads to IL-6 signaling, which is associated with MAPK cascade activation, PI3K cascade activation, and STAT3 activation (Heinrich PC et al. 2003; Hunter CA et al. 2015).

The oncostatin M receptor is associated with rare familial primary localized cutaneous amyloidosis (Arita K et al. 2008).

Furthermore, OSM signaling via the OSMR is thought to play an important role in bone turnover.

A decrease in OSMRβ activity has also been associated with adipose tissue inflammation and insulin resistance, which precedes obesity.

Hematopoiesis: OSMRβ receptor regulates hematopoiesis in vivo by stimulating stromal cells and hematopoietic progenitor cells-megakaryocyte and erythrocyte progenitor cells (Tanaka M et al 2003).

Cardiac diseases: OSMRβ is overexpressed in patients with chronic dilated cardiomyopathy. Furthermore, the activity of the cytokine controls the dedifferentiation and loss of sarcomeric structures in myocardial infarction and dilated cardiomyopathy.

Oncology: OSM receptor (OSMR) is overexpressed in squamous cell carcinomas of the cervix and is associated with unfavorable clinical outcomes and higher relative risk of death regardless of tumor stage (Ng G et al (2007).

OSM and OSMRβ are expressed together and lead to activation of STAT 3 in malignant human ovarian epithelial cells.

The OSMR-β promoter gene is highly methylated in primary colorectal cancer tissue and fecal DNA and represents a highly specific diagnostic biomarker for colorectal cancer.

1. Arita K et al (2008) Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis". American Journal of Human Genetics 82: 73-80.
2. Heinrich PC et al (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation". The Biochemical Journal 374: 1-20.
3. Hunter CA et al (2015) IL-6 as a keystone cytokine in health and disease. Nature Immunology 16: 448-457.
4. Kamiya A et al.(1999) Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. The EMBO Journal 18: 2127-36.
5. Ng G et al. (2007) Gain and overexpression of the oncostatin M receptor occur frequently in cervical squamous cell carcinoma and are associated with adverse clinical outcome. The Journal of Pathology 212: 325-334.
6. Tanaka M et al. (2003) Targeted disruption of oncostatin M receptor results in altered hematopoiesis. Blood 102: 3154-3162.
7. West NR et al (2018) The oncostatin M-stromal cell axis in health and disease". Scandinavian Journal of Immunology 88: e12694.