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

2021 ◽  
Author(s):  
Toyoshi Yanagihara ◽  
Kazuya Tsubouchi ◽  
Mahsa Gholiof ◽  
Sy Giin Chong ◽  
Kenneth E. Lipson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Lung Fibrosis ◽  
Tissue Growth ◽  
Tgf Β1

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.

scholarly journals Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis

1998 ◽  
Vol 275 (2) ◽  
pp. L365-L371 ◽  
Author(s):  
Joseph A. Lasky ◽  
Luis A. Ortiz ◽  
Boihoang Tonthat ◽  
Gary W. Hoyle ◽  
Miriam Corti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Mouse Strain ◽  
Lung Fibrosis ◽  
Tissue Growth ◽  
Lung Fibroblasts ◽  
Resistant Mouse ◽  
Tgf Β1 ◽  
Resistant Mouse Strain

Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-β1 (TGF-β1) response element. Because TGF-β1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-β1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF-β1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin-resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGF-β1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-β1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.

Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagen

2009 ◽  
Vol 60 (7) ◽  
pp. 2142-2155 ◽  
Author(s):  
Markella Ponticos ◽  
Alan M. Holmes ◽  
Xu Shi-Wen ◽  
Patricia Leoni ◽  
Korsa Khan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transcriptional Activation ◽  
Lung Fibrosis ◽  
Type I Collagen ◽  
Tissue Growth ◽  
Pivotal Role ◽  
Type I

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.

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