Oncostatin-M specific receptor subunit beta also known as theOncostatin M receptor (OSMR) , is one of the receptor proteins foroncostatin M, that in humans is encoded by theOSMRgene.[5][6]
OSMR is widely expressed across non-haematopoietic, hepatocytes, mesothelial cells, glial cells and epithelial cell types across various organs and mammary glands.[7] OSM receptor is abundantly expressed on endothelial and stromal/fibroblast cells in the lung of mice.[8]=
In vitro expression of OSMR in fetal hepatocytes is upregulated by OSM stimulation.[9]
OSMR expression has been shown to be induced by parathyroid hormone in osteoblasts and OSM.[10][11]
Intracellular cell signalling occurs as a consequence of extracellular binding of the ligandOSM to OSMR complexes, formed from dimerization with receptor subunits such asgp130. Activation of the OSMR-gp130 complex by OSM triggers Janus Kinase 1 (JAK1) andJak2 cross phosphorylation of tyrosine residues on the intracellular receptor domain. Downstream signaling activation of the OSMR-gp130 complex along the JAK1 pathway leads to IL-6 signalling which is linked with activation of the MAPK cascade,PI3K cascade andSTAT3 activation.[12][13]
OSM induced recruitment ofSHC to the OSMRβ sub-unit has been shown to enhanceRas/Raf/MAPK signaling and leadp38 andJNK activation.[14]
OSM signaling via the OSMR is believed to play an important role in bone turnover as Mice lacking the OSMR receptor have osteopetrotic phenotypes.[16] Lack of OSMRβ activity has also been linked to adipose tissue inflammation and insulin resistance preceding obesity.[17]
OSM in-vivo regulation of hematopoiesis, through stimulation of stromal cells & hematopoietic progenitors - megakaryocytic and erythrocytic progenitors, is carried out by the OSMRβ receptor.[18]
Inhibition of the OSMRβ extracellular subunit has been shown has been shown to prevent OSM-mediated down-regulation of myoglobin in cardiomyocytes and related apoptosis of cardiomyocytes in inflammatory heart failure.[19]
OSMRβ is not only overexpressed in patients with chronic dilated cardiomyopathy but has been shown to control dedifferentiation and loss of sarcomeric structures in myocardial infarction and dilated cardio myopathy.[20] OSM and OSMRβ mediated dedifferentiation has been shown to increase chances of survival after acute myocardial damage but poor survival rates and compromised pump functions in chronic disease states.[20]
OSMR activates STAT3 and transforming growth factor β (TGF-β) effector SMAD3 to regulate expression of genes responsible for inducing a mesenchymal/CSC phenotype.[21]
OSM-induced biological effects on breast tumor– derived cell lines were specifically mediated through the gp130/OSMRB complex.[22]
the OSM receptor (OSMR) is overexpressed in cervical squamous cell carcinomas and, independent of tumor stage, is associated with adverse clinical outcomes and higher relative risk of death.[23]
OSM and OSMRβ are co-expressed and lead to STAT 3 activation malignant human ovarian epithelial cells.[24]
The OSMR β promoter gene is highly methylated in primary Colorectal Cancer tissues and fecal DNA, it is a highly specific diagnostic biomarker of Colorectal Cancer.[25]
^Ng G, Winder D, Muralidhar B, Gooding E, Roberts I, Pett M, Mukherjee G, Huang J, Coleman N (July 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 (3):325–34.doi:10.1002/path.2184.PMID17516585.S2CID21134882.
^Savarese TM, Campbell CL, McQuain C, Mitchell K, Guardiani R, Quesenberry PJ, Nelson BE (March 2002). "Coexpression of oncostatin M and its receptors and evidence for STAT3 activation in human ovarian carcinomas".Cytokine.17 (6):324–34.doi:10.1006/cyto.2002.1022.PMID12061840.
