Oncostatin M

Oncostatin-M (OSM) is associated with antitumor necrosis factor (anti-TNF)-α resistance in inflammatory bowel disease (IBD) and fibrosis in inflammatory diseases. We studied the expression of OSM and its receptors (OSMR, gp130) on intestinal subepithelial myofibroblasts (SEMFs) and the effect of OSM stimulation on SEMFs.

The mRNA and protein expression of OSM, OSMR, gp130, and several fibrotic and chemotactic factors were studied in mucosal biopsies and isolated human intestinal SEMFs of patients with IBD and healthy controls (HCs) and in a model of human intestinal organoids (HIOs). Subepithelial myofibroblasts and HIOs were stimulated with OSM and interleukin (IL)-1α/TNF-α. RNAseq data of mucosal biopsies were also analyzed.

Oncostatin-M receptors and gp130 were overexpressed in mucosal biopsies of patients with IBD (P < .05), especially in inflamed segments (P < .05). The expression of OSM, OSMR, and gp130 in SEMFs from HCs was increased after stimulation with IL-1α/TNF-α (P < .001; P < .01; P < .01). The expression of CCL2, CXCL9, CXCL10, and CXCL11 was increased in SEMFs from patients with IBD and HCs after stimulation with OSM in a dose-dependent manner (P < .001; P < .05; P < .001; P < .001) and was further increased after prestimulation with IL-1α/TNF-α (P < .01 vs OSM-alone). Similar results were yielded after stimulation of HIOs (P < .01). Oncostatin-M did not induce the expression of collagen I, III, and fibronectin. Oncostatin-M receptor expression was positively correlated with CCL2, CXCL9, CXCL10, and CXCL11 expression in mucosal biopsies (P < .001; P < .001; P = .045; P = .033).

Human SEMFs overexpress OSMR in an inflammatory microenvironment. Oncostatin-M may promote inflammation in IBD via its stimulatory effects on SEMFs, which primarily involve chemoattraction of immune cells to the intestinal mucosa.

Polycystic ovary syndrome (PCOS) is a primary endocrinological disorder in women of reproductive age that is characterized by androgen excess and ovulatory irregularities. This syndrome is associated with adipose tissue dysfunction, an elevated risk of insulin resistance, hyperinsulinemia, obesity, and type 2 diabetes. Adipocyte dysfunction affects the secretion of adipokines and pro-inflammatory cytokines. Nevertheless, adipose tissue is not an exclusive source of adipokines as it can also be produced locally by reproductive tissues. Although adipokines have been recognized in the development of PCOS, the role of oncostatin M (OSM), a multifaceted adipokine, remains unclear. Current evidence suggests that this cytokine is associated with key aspects of the syndrome, including obesity, insulin resistance, hyperandrogenism, and inflammation. However, the data are often contradictory, likely due to variations in study designs, methodologies, and species differences. By investigating the link between OSM and PCOS-associated issues, this review identified the potential role of this adipokine in PCOS pathogenesis. This underscores the need for further research to clarify its predominant effects and assess its relevance as a therapeutic target.