scholarly journals Connective tissue growth factor promotes temozolomide resistance in glioblastoma through TGF-β1-dependent activation of Smad/ERK signaling

2017 ◽  
Vol 8 (6) ◽  
pp. e2885-e2885 ◽  
Author(s):  
Huijun Zeng ◽  
Zhao Yang ◽  
Ningbo Xu ◽  
Boyang Liu ◽  
Zhao Fu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Erk Signaling ◽  
Tgf Β1

Connective tissue growth factor antagonizes transforming growth factor-β1/Smad signalling in renal mesangial cells

2011 ◽  
Vol 441 (1) ◽  
pp. 499-510 ◽  
Author(s):  
Helen C. O'Donovan ◽  
Fionnuala Hickey ◽  
Derek P. Brazil ◽  
David H. Kavanagh ◽  
Noelynn Oliver ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Transcriptional Responses ◽  
Cell Contractility ◽  
Tgf Β1

The critical involvement of TGF-β1 (transforming growth factor-β1) in DN (diabetic nephropathy) is well established. However, the role of CTGF (connective tissue growth factor) in regulating the complex interplay of TGF-β1 signalling networks is poorly understood. The purpose of the present study was to investigate co-operative signalling between CTGF and TGF-β1 and its physiological significance. CTGF was determined to bind directly to the TβRIII (TGF-β type III receptor) and antagonize TGF-β1-induced Smad phosphorylation and transcriptional responses via its N-terminal half. Furthermore, TGF-β1 binding to its receptor was inhibited by CTGF. A consequent shift towards non-canonical TGF-β1 signalling and expression of a unique profile of differentially regulated genes was observed in CTGF/TGF-β1-treated mesangial cells. Decreased levels of Smad2/3 phosphorylation were evident in STZ (streptozotocin)-induced diabetic mice, concomitant with increased levels of CTGF. Knockdown of TβRIII restored TGF-β1-mediated Smad signalling and cell contractility, suggesting that TβRIII is key for CTGF-mediated regulation of TGF-β1. Comparison of gene expression profiles from CTGF/TGF-β1-treated mesangial cells and human renal biopsy material with histological diagnosis of DN revealed significant correlation among gene clusters. In summary, mesangial cell responses to TGF-β1 are regulated by cross-talk with CTGF, emphasizing the potential utility of targeting CTGF in DN.

Connective-Tissue Growth Factor (CTGF/CCN2) Contributes to TGF-β1-Induced Lung Fibrosis

2020 ◽  
Author(s):  
Toyoshi Yanagihara ◽  
Sy Giin Chong ◽  
Mahsa Gholiof ◽  
Kenneth E. Lipson ◽  
Quan Zhou ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Connective Tissue Growth Factor ◽  
Lung Fibrosis ◽  
Adenovirus Vector ◽  
Tissue Growth ◽  
Inhibitory Antibody ◽  
Tgf Β1

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive and excessive accumulation of myofibroblasts and extracellular matrix in the lung. Connective-tissue growth factor (CTGF) is known to exacerbate pulmonary fibrosis in radiation-induced lung fibrosis, and in this study, we show the upregulation of CTGF from a rat lung fibrosis model induced by adenovirus vector encoding active TGF-β1 (AdTGF-β1), and also in patients with IPF. The expression of CTGF was upregulated in vascular smooth muscle cells cultured from fibrotic lungs on days 7 or 14 as well as endothelial cells sorted from fibrotic lungs on day 14 or 28 respectively. These findings suggest the role of different cells in maintaining the fibrotic phenotype during fibrogenesis. Treatment of fibroblasts with recombinant CTGF along with TGF-β increases pro-fibrotic markers in fibroblasts, confirming the synergistic effect of recombinant CTGF with TGF-β in inducing pulmonary fibrosis. Also, fibrotic extracellular matrix upregulated the expression of CTGF, as compared to normal extracellular matrix, suggesting that not only profibrotic mediators but also a profibrotic environment contributes to fibrogenesis. We also showed that pamrevlumab, a CTGF inhibitory antibody, partially attenuates fibrosis in the model. These results suggest that pamrevlumab could be an option for the treatment of pulmonary fibrosis.

PKCδ as a regulator for TGF-β-stimulated connective tissue growth factor production in human hepatocarcinoma (HepG2) cells

2013 ◽  
Vol 456 (1) ◽  
pp. 109-118 ◽  
Author(s):  
Su Jin Lee ◽  
Jeong Han Kang ◽  
Soo Young Choi ◽  
Oh-Shin Kwon
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Hepg2 Cells ◽  
Critical Role ◽  
Gene Induction ◽  
Tissue Growth ◽  
Factor Production ◽  
Growth Factor Production ◽  
Tgf Β1

In the present study, we demonstrated that PKCδ-stimulated RhoA/ROCK activation resulted in a reduction in PPM1A, thereby up-regulating Smad-dependent gene induction for extended periods. These findings indicated that PKCδ plays a critical role in TGF-β1-induced CTGF production in HepG2 cells.

scholarly journals Kinetics of Connective Tissue Growth Factor Expression during Experimental Proliferative Glomerulonephritis

2001 ◽  
Vol 12 (3) ◽  
pp. 472-484
Author(s):  
YASUHIKO ITO ◽  
ROEL GOLDSCHMEDING ◽  
RICHARD J. BENDE ◽  
NIKE CLAESSEN ◽  
M. ANWAR CHAND ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Connective Tissue ◽  
Mrna Expression ◽  
Connective Tissue Growth Factor ◽  
Mesangial Cells ◽  
Tissue Growth ◽  
Proliferative Glomerulonephritis ◽  
Kinetics Of ◽  
Tgf Β1

Abstract. Connective tissue growth factor (CTGF) is a member of the CCN family of immediate early genes, which are involved in cell proliferation, migration, and matrix production. Recently, CTGF was observed to be strongly upregulated in human proliferative and fibrogenic renal disease. 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. CTGF expression in cultured rat mesangial cells and glomerular visceral epithelial cells (GVEC) was studied in response to transforming growth factor β (TGF-β), an essential pathogenetic factor in this model. In normal rat kidneys, only some GVEC expressed CTGF mRNA. In anti—Thy-1.1 nephritis, CTGF mRNA expression was strongly increased in extracapillary and mesangial proliferative lesions and in areas of periglomerular fibrosis. Early glomerular CTGF overexpression in GVEC coincided with a striking upregulation of TGF-β2 and to a lesser extent of TGF-β3. Glomerular CTGF mRNA expression was maximal at day 7, in association with increased TGF-β1 mRNA and protein expression. CTGF mRNA overexpression by parietal epithelial cells preceded the periglomerular appearance of α-smooth muscle actin—positive fibroblasts. In cultured mesangial cells, TGF-β1, -β2, and -β3 transiently increased the CTGF/glyceraldehyde phosphate dehydrogenase mRNA ratio up to threefold versus control at 4 h. In GVEC, upregulation of CTGF mRNA by these TGF-β isoforms was more sustained, being 8- to 16-fold versus control at 24 h. The kinetics of CTGF expression strongly suggest a role in glomerular repair, possibly downstream of TGF-β, in this model of transient renal injury.

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