Early Differential Expression of Oncostatin M in Obstructive Nephropathy

Abstract

Interstitial fibrosis plays a major role in progression of renal diseases. Oncostatin M (OSM) is a cytokine that regulates cell survival, differentiation, and proliferation. Renal tissue from patients with chronic obstructive nephropathy was examined for OSM expression. The elevated levels in diseased human kidneys suggested possible correlation between OSM level and kidney tissue fibrosis. Indeed, unilateral ureteral obstruction (UUO), a model of renal fibrosis, increased OSM and OSM receptor (OSM-R) expression in a time-dependent manner within hours following UUO. In vitro, OSM overexpression in tubular epithelial cells (TECs) resulted in epithelial-myofibroblast transdifferentiation. cDNA microarray technology identified up-regulated expression of immune modulators in obstructed compared with sham-operated kidneys. In vitro, OSM treatment up-regulated CC chemokine ligand CCL7, and CXC chemokine ligand (CXCL)-14 mRNA in kidney fibroblasts. In vivo, treatment of UUO mice with neutralizing anti-OSM antibody decreased renal chemokines expression. In conclusion, OSM is up-regulated in kidney tissue early after urinary obstruction. Therefore, OSM might play an important role in initiation of renal fibrogenesis, possibly by inducing myofibroblast transdifferentiation of TECs as well as leukocyte infiltration. This process may, in turn, contribute in part to progression of obstructive nephropathy and makes OSM a promising therapeutic target in renal fibrosis.

OSMR gene effect on the pathogenesis of chronic autoimmune Urticaria via the JAK/STAT3 pathway

“…Consequently, it was revealed that OSMR gene silencing can obstruct the development of CAU by inhibiting the JAK/STAT3 signaling pathway, as increased proliferation, migration and decreased apoptosis of epithelial cells were observed in the OSMR-siRNA group. OSM, is a cytokine capable of modulating cell survival and proliferation, and the over-expression of OSM could result in transdifferentiation of epithelial-myofibroblast (Elbjeirami et al, 2010 ). In line with the findings of the current study, it was reported that over-expression of OSM in tubular epithelial cells might aggravate mucosal epithelial barrier dysfunction (Pothoven et al, 2015 ).…”

Lats1 and Lats2 are required for the maintenance of multipotency in the Müllerian duct mesenchyme

“…S3), all of which are associated with myofibroblast functions (Klingberg et al, 2013;Gerarduzzi and Di Battista, 2017). Furthermore, six out of the 20 most highly upregulated genes have been associated with myofibroblast activation, differentiation or function (Table 1, genes in bold) (Elbjeirami et al, 2010;Garrett et al, 2004;Gomez et al, 2016;Lenga et al, 2008;Lipson et al, 2012;Mifflin et al, 2002;Nightingale et al, 2004;Sobral et al, 2011). RT-qPCR analyses were performed for selected genes to confirm the microarray analyses (Fig.…”

Synergistic induction of CCL2/MCP-1 expression driven by oncostatin M and IL-1βin human proximal tubular cells depends on STAT3 and p65 NFκB/RelA

“…Although unilateral ureteral obstruction (UUO), a model of renal fibrogenesis, increased OSM and OSMR expression in a time‐dependent manner (Elbjeirami et al. ), we obtained evidence from preliminary microarray analysis of OSM‐stimulated human PTC that this IL‐6 family cytokine might also have antifibrotic effects (Pollack et al. ).…”

“…Chemokines such as CCL2 and their receptors are key mediators involved in inflammatory cell interactions and recruitment, cellular adhesion, differentiation, and tissue damage in the setting of diabetic nephropathy (Navarro-Gonz alez et al 2011 ;Kanasaki et al 2013;Wada and Makino 2013). Renal proximal tubular cells (PTC) represent important proinflammatory/profibrotic effector cells for OSM and several other proinflammatory/profibrotic ligands in these processes (Nightingale et al 2004;Pollack et al 2007;Elbjeirami et al 2010;Sark€ ozi et al 2011Sark€ ozi et al , 2012Tang and Lai 2012). Thus, we next studied mRNA expression of the chemokine CCL2 in human PTC selectively stimulated with IL-1b, TNF-a, or TGF-b1.…”

“…These effects were associated with OSM-induced human PTC scattering in threedimensional collagen matrices after long-term incubation, all together suggesting that OSM is able to induce cellular events indicative of tubular epithelial-mesenchymal transition (EMT) (Pollack et al 2007). Although unilateral ureteral obstruction (UUO), a model of renal fibrogenesis, increased OSM and OSMR expression in a time-dependent manner (Elbjeirami et al 2010), we obtained evidence from preliminary microarray analysis of OSM-stimulated human PTC that this IL-6 family cytokine might also have antifibrotic effects (Pollack et al 2007). Indeed, we were able to show that OSM represents an inhibitor of TGF-b1-induced matricellular protein expression, namely of CTGF, SPARC, tenascin C (TNC) and thrombospondin-1 (TSP-1) (Sark€ ozi et al 2011).…”