Major signaling pathways and effectors in liver fibrosis Pathway Effectors Growth factor signaling PDGF, TGF-[alpha], EGF, VEGF Fibrogenic signaling pathway TGF-[beta]1 Chemokine pathways CCR5, CCR1, CXCL4, CXCL9, CXCR3 Adipokine pathways Leptin, adiponectin Neuroendocrine pathways Cannabinoid and opioid signaling, thyroid hormones, serotonin CCR: C-C chemokine receptor; CXCL: CXC chemokine ligand; CXCR
: CXC chemokine receptor; EGF: epidermal growth factor; PDGF: platelet-derived growth factor; TGF: transforming growth factor; VEGF: vascular endothelial growth factor
They exert their effects through the CXC receptors (CXCR
), CC receptors (CCR), and C[X.sub.3]CR1 receptor, respectively .
(45) Cyclophosphamide reverses the increased (IFN[gamma]) production by CD8+ T-cells and increases the percentage of CCR4+ T-cells that produce high levels of IL-4 and decreases interferon gamma producing CCR5+ and CXCR
Desarmenien et al., "The chemokine SDF-1/CXCL12 modulates the firing pattern of vasopression neurons and counteracts induced vasopressin release through CXCR
," Proceedings of the National Academy of Sciences of the United States of America, vol.
Target genes for HIF are those encoding for vascular endothelial growth factor (VEGF) and the chemokine receptor Cxcr
(4,15) and proteins involved in activation of proliferation (reviewed in Maxwell (16)).
According to the chemokine subclass, chemokine receptors, a large family of G protein-coupled receptors (GPCRs) , are classified into CR, CCR, CXCR
, and CX3CR with a large variety of distribution and function in AAA .
Monocytes are mainly mobilized by CC-chemokines that bind to CC-receptors (CCR), whereas they normally do not respond to CXC-chemokines as they are lacking their cognate CXC-receptors (CXCR
) [12, 14, 15].
CXCL12 is a ligand of the C-X-C chemokine receptor type (CXCR
) 4, and through it, [ESC.sub.cyst] may further increase levels of inflammation in the pelvic cavity by recruiting CXCR4-positive immune cells .
Acting as cytokine, HMGB1 transduces signals and coordinates cellular activities through (RAGE), TLR2, TLR4, TIM-3, chemokine CXC receptor (CXCR
)-4, and CD24-Siglec G/10 .
However, HIF-2[alpha], TWIST, and CXCR
protein expression was significantly correlated with LNM; PTC patients with LNM showed higher protein expression of these three molecules than those without LNM (P < 0.001 for all the three molecules).