Disease relevance of Ctgf

• Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis [1].
• Using unilateral ureteral obstruction (UUO) in rats, we analyzed gene expression of TGF-beta1, CTGF, and fibronectin [1].
• CONCLUSIONS: These results indicate that CTGF expressed in the glomeruli is upregulated in the early stage of STZ-induced diabetic nephropathy in rats, and could be a critical mediator of the development of diabetic glomerulosclerosis [2].
• The CTGF mRNA levels seemed to peak within the second week of the urethral obstruction and correlate well with increased type I collagen mRNA [3].
• Connective tissue growth factor in indomethacin-induced rat gastric ulcer [4].

High impact information on Ctgf

• Connective tissue growth factor (CCN2) in rat pancreatic stellate cell function: integrin alpha5beta1 as a novel CCN2 receptor [5].
• Homology analysis indicates that rCop-1 belongs to an emerging cysteine-rich growth regulator family called CCN, which includes connective-tissue growth factor, CYR61, CEF10 (v-src inducible), and the product of the nov proto-oncogene [6].
• In contrast, elevation of cAMP levels within the target cells by a variety of methods blocked the induction of CTGF by TGF-beta [7].
• We have investigated the signaling pathways controlling the TGF-beta induction of connective tissue growth factor (CTGF) gene expression [7].
• These and other studies in monolayer cultures suggest that the CTGF restriction point in the cell cycle is distinct from the adhesion-dependent arrest point [7].

Chemical compound and disease context of Ctgf

• To explore its involvement in early diabetic nephropathy, we investigated the time course of CTGF gene expression and its regulation in streptozotocin (STZ)-induced diabetic rat kidney [2].
• Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor [8].
• This novel finding suggests that CTGF may be a mediator of the profibrogenic effects of Ang II in vascular diseases [9].
• Connective tissue growth factor-mediated angiotensin II-induced hypertrophy of proximal tubular cells [10].
• In rats with immune complex nephritis, renal overexpression of CTGF was diminished by the ACE inhibitor quinapril, correlated with a diminution in fibrosis [11].

Biological context of Ctgf

• CTGF antisense ODN transfected into cultured renal fibroblasts significantly attenuated TGF-beta-stimulated upregulation of fibronectin mRNA and protein compared with control ODN transfection, together with inhibited synthesis of type I collagen [1].
• In cultured mesangial cells, aspirin treatment abolished high glucose-stimulated CTGF upregulation [2].
• CTGF silencing by siRNA prevented the down-regulation of BCL-2L expression induced by TGF-beta, had no effect on the BAX expression [12].
• Connective tissue growth factor is responsible for transforming growth factor-beta-induced peritoneal mesothelial cell apoptosis [12].
• We have studied the expression of CTGF in a rat wound-healing model using Northern blot, in situ hybridization, and immunohistochemistry [13].

Anatomical context of Ctgf

• We further investigated the effect of blockade of endogenous CTGF on TGF-beta-induced fibronectin expression in cultured rat renal fibroblasts by antisense oligodeoxynucleotide (ODN) treatment [1].
• Evidence for low-density lipoprotein-induced expression of connective tissue growth factor in mesangial cells [14].
• By in situ hybridization, CTGF mRNA was detected mainly in the interstitial fibrotic areas and tubular epithelial cells as well as in parietal glomerular epithelial cells in the obstructed kidney [1].
• Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells [15].
• In addition, we evaluated the effect of aldosterone and spironolactone on CTGF and collagen production in cultured cells [16].

Associations of Ctgf with chemical compounds

• Roles of connective tissue growth factor and prostanoids in early streptozotocin-induced diabetic rat kidney: the effect of aspirin treatment [2].
• In cultured MC and PTC, aldosterone induced significant increases in CTGF gene expression and protein synthesis associated with increased collagen synthesis, which was abolished by prior treatment with spironolactone [16].
• Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant [17].
• Effect of cyclosporine and sirolimus on the expression of connective tissue growth factor in rat experimental chronic nephrotoxicity [18].
• Northern blot analysis showed expression of TGF-beta mRNA on days 1 and 3 after indomethacin administration, expression of CTGF mRNA on days 1, 3 and 7 and type III collagen mRNA expression on days 1, 3, 7 and 12, respectively [4].

Regulatory relationships of Ctgf

• After UUO, CTGF mRNA expression in the obstructed kidney was significantly upregulated subsequent to TGF-beta1, followed by marked induction of fibronectin mRNA [1].
• Additionally, AGE-induced mitogenesis and type I collagen protein expression were dependent on leptin-induced CTGF [19].
• We further studied the mechanisms involved in the regulation of MMP-2 mRNA levels and found that the AP-2 transcription factor is responsible for most of the CTGF-induced MMP-2 transcription [15].
• CTGF is able to promote VSMC proliferation and migration and influences the composition of extracellular matrix [15].
• This in vitro observation of CTGF mRNA down-regulation coinciding with FSH-induced granulosa cell maturation is substantiated by studies of in vivo ovarian CTGF expression in FSHbeta knockout mice [20].

Other interactions of Ctgf

• Thus, the effects of AGE (150 microg/ml) and leptin on mitogenesis, CTGF and collagen expression in NRK-49F cells were determined [19].
• In NRK-49F cells, IGF-I increased the activity of CTGF towards the expression of Col alpha1III [21].
• The previously identified basal control element-1 (BCE-1) site, but not Sp1 contributes to basal CTGF promoter activity [22].
• Connective tissue growth factor (CTGF), a TGF-beta-inducible molecule, has recently been reported to promote fibroblast proliferation, migration, adhesion and extracellular matrix formation, both in vivo and in vitro [23].
• The protein kinase A antagonist H89 abolished the inhibitory effect of PTX on Smad3/4-dependent CTGF transcription, whereas dibutyryl cAMP and forskolin recapitulated the inhibitory effect [8].

Analytical, diagnostic and therapeutic context of Ctgf

• METHODS: Northern blot analysis for CTGF, TGF-beta, and fibronectin expression was performed in the glomeruli of STZ-induced diabetic rats from 3 days to 12 weeks after the induction of diabetes, together with histological examination [2].
• Regulation and actions of CTGF were studied in in vitro cell culture models [21].
• These results suggest that the antifibrotic effects of spironolactone may be mediated by CTGF through a TGF-beta1-independent pathway in this animal model of diabetic nephropathy [16].
• Moreover, the significant increases of CTGF and TGF-beta1 in the HCV core-expressing cells were observed by either Northern or Western blot analysis [24].
• In immunohistochemistry, all growth factors were expressed by fibroblast-like cells, macrophage-like cells, and blood vessels but CTGF-positive cells were fewer and were more restricted on days 5 and 7 [13].

References