Osteopontin: A Protective Mediator of Cardiac Fibrosis?

Abstract

O steopontin (OP) is a multifunctional cytokine and adhesion protein that contains an RGD (argininglycin-aspartate) binding sequence that enables it to interact with several integrins, CD44 variants, and other adhesion receptors. OP receptor binding then directly or indirectly activates intracellular signaling pathways, mediating its effects on cell-matrix and cell-cell interactions. OP is increased in response to pro-inflammatory cytokines and mechanical strain in various cell types, 1 and the function of its secreted protein can be altered by proteases, including thrombin. 2 Thus, OP can exists as an immobilized matrix molecule (eg, in bone, atherosclerotic plaques, or calcified heart valves) or as soluble cytokine.Cell signaling by OP is predominantly mediated through integrin engagement. Cleavage of OP by thrombin exposes integrin binding sites 2 (eg, for ␣ 9 ␤ 1 ), which are important for OP-mediated adhesion/migration. OP is chemotactic for various cell types, most notably monocytes/macrophages, which are attracted to sites of injury and inflammation. The bestcharacterized OP-induced signal pathway is the integrinstimulated FAK-Src-Rho pathway in osteoclasts. 1 However, identification and dissection of signal transduction pathways are complicated by the fact that OP potentially binds to several cell surface receptors.

Osteopontin expression in normal and fibrotic liver. Altered liver healing in osteopontin-deficient mice

“…Therefore, the liver response to damage in osteopontin-deficient mice appears quite distinctive. However, similarly to our data in liver, it has been recently suggested that osteopontin could be a protective mediator of cardiac fibrosis [33]. The mechanism of CCl 4 -induced fibrogenesis involves a toxicity of this compound for hepatocytes whereby CCl 4 induces hepatocyte necrosis following its metabolism to a toxic metabolite [34].…”

Oligo-fucoidan prevents renal tubulointerstitial fibrosis by inhibiting the CD44 signal pathway

“…Increased HA causes an aggressive phenotype leading to severe lung fibrosis after bleomycin-induced injury38. OPN is an immobilized matrix phosphorylated glycoprotein39 that plays a key role in diabetic nephropathy40. The transfection of OPN siRNA in vivo inhibited the progression of chronic allograft nephropathy41.…”

MicroRNA-328 Inhibits Renal Tubular Cell Epithelial-to-Mesenchymal Transition by Targeting the CD44 in Pressure-Induced Renal Fibrosis

“…Increased HA also produced an aggressive phenotype leading to severe lung fibrosis and death after bleomycin-induced injury [43]. OPN is a phosphorylated glycoprotein that exists as an immobilized matrix protein and a cytokine [45]. Recent evidence suggests that OPN plays a key role in fibrosis [46], [47].…”