Disease relevance of CTGF

• In this study, we investigated the role of CTGF in rhabdomyosarcoma [1].
• Therefore, the cooperation between CTGF and IGF-I might be involved in glucose-induced matrix accumulation in tubulointerstitial fibrosis and might contribute to the pathogenesis of diabetic nephropathy [2].
• In addition, the lymphoblastic leukemia T cell line (Loucy) that possesses characteristics typical of gammadelta-T cells was used as a model to evaluate the regulation of CTGF gene expression [3].
• INTRODUCTION: Connective tissue growth factor (CTGF/CCN2) is a mediator of local angiogenesis induced by breast cancer, but its role in osteolytic metastasis has not been evaluated [4].
• By in situ hybridization and reverse transcriptase-PCR, the expression of CTGF was investigated in experimental proliferative glomerulonephritis induced by injection of anti-Thy-1.1 antibody in the rat [5].
• Ovarian cancer tended to lack CTGF expression more frequently in the earlier stages (stages I and II) than the advanced stages (stages III and IV) [6].
• We conclude that hypoxia increases cellular CTGF mRNA levels and CTGF protein secretion from cultured trophoblasts, likely in a HIF1alpha-dependent manner [7].
• These findings demonstrate that plasma CTGF is a risk marker of diabetic renal and vascular disease [8].

Psychiatry related information on CTGF

• After the cells were rested in serum-free medium for 24 h, the dose and time response of CTGF mRNA expression to Ang II stimulation was observed by RT-PCR, and protein synthesis was observed by Western blotting [9].
• Connective tissue growth factor in Alzheimer's disease [10].

High impact information on CTGF

• Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFbeta signaling [11].
• The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family [12].
• Here we show that Iloprost, acting by elevation of cAMP, blocks the induction of CTGF and the increase in collagen synthesis in fibroblasts exposed to TGF-beta [13].
• By sampling dermal interstitial fluid using a suction blister device, we show that CTGF levels are greatly elevated in the dermis of scleroderma patients compared with healthy controls and that Iloprost infusion causes a marked decrease in dermal CTGF levels [13].
• The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP [13].

Chemical compound and disease context of CTGF

• Levels of NH2-terminal CTGF were also greater in vitreous samples from diabetic patients with vitreous hemorrhage compared with samples from nondiabetic patients with vitreous hemorrhage (P=0.02) [14].
• The CTGF siRNA treatment markedly reduced serum procollagen type III, hepatic hydroxyproline and liver fibrosis staging [15].
• Immunohistochemistry studies of gingival overgrowth tissue samples indicate for the first time detectable levels of CTGF protein in Dilantin-induced hyperplasia tissues also positive for TGF-beta1 [16].
• These associations suggest a possible role for CTGF in promoting development of fibrotic lesions in phenytoin-induced gingival overgrowth [17].
• CONCLUSIONS: The data from the present study show significantly higher CTGF staining in phenytoin-induced gingival overgrowth tissues compared to controls, cyclosporin A-, or nifedipine-induced gingival overgrowth [17].

Biological context of CTGF

• Two members of the family (CYR61 and CTGF) are positive regulators of cell proliferation, whereas NOVH and two other members (ELM1 and RCOP-1) exhibit features of negative regulators of growth [18].
• Because monocyte adhesion and transmigration are important for atherosclerosis, wound healing, and inflammation, we examined the interaction of THP-1 monocytic cells and isolated peripheral blood monocytes with Cyr61 and CTGF [19].
• Both treatments inhibited rhabdomyosarcoma cell growth, suggesting the existence of a new autocrine loop based on CTGF [1].
• In this study, we examined the ability of TNFalpha to modulate CTGF gene expression [20].
• Northern blot further confirmed the Cyr61 and CTGF up-regulation is in a dose- and time-dependent manner [21].

Anatomical context of CTGF

• THP-1 cells and monocytes adhered to Cyr61- or CTGF-coated wells in an activation-dependent manner and this process was mediated primarily through integrin alpha(M)beta(2) [19].
• Human rhabdomyosarcoma cells of the embryonal (RD/12, RD/18, CCA) and the alveolar histotype (RMZ-RC2, SJ-RH4, SJ-RH30), rhabdomyosarcoma tumor specimens, and normal skeletal muscle cells expressed CTGF [1].
• Thus, we suspect that the high level of constitutive CTGF expression in scleroderma fibroblasts and its inability to respond to negative regulatory cytokines may contribute to the excessive scarring of skin and internal organs in patients with scleroderma [20].
• CTGF does not appear to act on epithelial cells or immune cells [22].
• The addition of CTGF to primary mesangial cells induced fibronectin production, cell migration, and cytoskeletal rearrangement [23].

Associations of CTGF with chemical compounds

• Moreover, we observed a partial inhibition in glucose-induced collagen secretion with neutralizing anti-CTGF antibodies, thereby demonstrating for the first time the involvement of endogenous CTGF in glucose-induced effects in human renal fibroblasts [2].
• Cycloheximide did not block the large TGF-beta stimulation of CTGF gene expression, indicating that it is directly regulated by TGF-beta [24].
• Only PGF2alpha up-regulated CTGF mRNA expression in the cat iris [21].
• Because prostamide receptors are, to date, defined only at the pharmacological level, Bimatoprost effects on Cyr61 and CTGF were studied in the isolated feline iris sphincter preparation, a tissue highly responsive to prostamides [21].
• Activation of prostaglandin EP2 receptors (Gs-coupled) also up-regulated Cyr61 but not CTGF mRNA expression in the isolated cat iris [21].

Physical interactions of CTGF

• The interaction of VEGF165 with CTGF inhibited the binding of VEGF165 to the endothelial cells and the immobilized KDR/IgG Fc; that is, a recombinant protein for VEGF165 receptor [25].
• Gao and Brigstock assign to CCN2 module 3 the capacity to mediate binding to low-density-lipoprotein receptor-related protein (LRP), which was previously reported to interact with CCN2 and to be involved in various types of signalling [26].
• It has been demonstrated that human CTGF specifically binds IGFs with low affinity and is considered to be a member of the IGFBP superfamily (IGFBP-rP2) [27].
• CT domain of CCN2/CTGF directly interacts with fibronectin and enhances cell adhesion of chondrocytes through integrin alpha5beta1 [28].

Regulatory relationships of CTGF

• TGF-beta promoted fibroblast CTGF, fibronectin, and type I collagen expression and enhanced fibroblast contractile activity [29].
• CONCLUSIONS: TA reduced VEGF expression and induced CTGF expression in ARPE19 cells exposed to oxidative stress, and conditioned medium from these cells inhibited tube formation by HUVECs [30].
• It is conceivable that the crosstalk between Smad3 and ERK1/2 signaling cascades plays an important role in regulating CTGF expression, e.g., in wound repair and tissue fibrosis and could be exploited in therapeutic targeting of fibrotic conditions [31].
• Interleukin-4 regulates connective tissue growth factor expression in human lung fibroblasts [32].
• To elucidate further the molecular mechanism by which PPAR gamma inhibits CTGF expression, an approximately 2-kilobase pair CTGF promoter was cloned [33].
• We previously demonstrated that JNK1 phosphorylation by TGFbeta1 is also critical for TGFbeta1-induced CCN2/CTGF expression, and forskolin partially reduces levels of phosphorylated JNK1 [34].

Other interactions of CTGF

• Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features [35].
• Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165 [36].
• RESULTS: In glomeruli of normal kidneys, mRNA and protein levels for THBS1, latent-TGFB1 and CTGF were low [37].
• Glomerular expression of thrombospondin-1, transforming growth factor beta and connective tissue growth factor at different stages of diabetic nephropathy and their interdependent roles in mesangial response to diabetic stimuli [37].
• Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-beta-induced expression of connective tissue growth factor in human fibroblasts [31].
• The results do not reveal a relevant interrelation between TGF-beta function and CTGF/CCN2 expression in hepatic stellate cells, which is in contrast to hepatocytes [38].
• Genetic and pharmacological manipulations suggested that the CTGF-mediated S100A4 upregulation was dependent on ERK1/2 activation, with expression levels of CTGF and S100A4 being closely correlated with human breast tumors [39].

Analytical, diagnostic and therapeutic context of CTGF

• In addition, Western blot analysis of human gammadelta-T cell lysates prepared 4 days following stimulation with IL-15 and TGF-beta1 revealed a 38-kDa CTGF protein in cell lysates of human gammadelta-T cells [3].
• METHODS: CTGF gene and protein expression, as well as protein levels of CTGF in the synovium, after treatment with the TSP-1-derived peptide were studied in the peptidoglycan-polysaccharide animal model of erosive arthritis [40].
• Immunofluorescence studies showed that the mean area fraction of CTGF immunoreactivity in the peptide-treated group of animals was significantly less than that in the untreated group [40].
• By immunohistochemistry, CTGF protein was localized at high levels in the same cell types as CTGF mRNA [41].
• RESULTS: RT-PCR analysis demonstrated the expression of CTGF mRNA in cultured primay HPMCs isolated from spent peritoneal effluent [42].

References