Figure 6
From: Role of HCV Core gene of genotype 1a and 3a and host gene Cox-2 in HCV-induced pathogenesis
HCV Core protein affects on the cellular genes involved in oxidative stress, apoptosis, cell survival and angiogenesis. Schematic diagram illustrating the role of HCV Core on cellular genes. In HCV, normal angiogenesis process can be malignant by deregulation of genes involved in this pathway. HCV Core protein up-regulates NFKB, which further up-regulates iNOS and COX-2 pathways, and inhibit apoptosis by blocking bad and caspase pathway. COX-2 up-regulation leads to apoptosis inhibition via VEGF pathway. VEGF can trigger angiogenesis either by iNOS or AKT activation. AKT singling also up-regulates AR and inhibit BAD and Caspase9 that leads to angiogenesis via cell survival. AKT also have direct impact on iNOS regulation that also escorts to angiogenesis. We corroborated that using siRNA against Core, or Cox-2 either alone or in combination can block angiogenesis directly or via Cox-2 reduced expression. PLC, PhosphoLipase; DAG, diacylglycerol; PKC, protein kinase C; iNOS, inducible nitric oxide synthase; NO, nitric oxide; VEGF, vascular endothelial growth factor; PGE2, prostaglandin E2; COX-2, cyclooxygenase-2; NFKB, nuclear factor kappa-B; P13K, phosphoinositide-3-kinase; PIP3, phosphatidylinositol 3,4,5-trisphosphate; PRAS40, proline-rich Akt substrate of 40 kDa; AR, Aldose reductase; BAD, Bcl-XL/Bcl-2-associated death promoter; CASPASE9, apoptosis-related cysteine peptidase.