scholarly journals ALK-5 Mediates Endogenous and TGF-β1–Induced Expression of Connective Tissue Growth Factor in Embryonic Lung

2007 ◽  
Vol 36 (5) ◽  
pp. 552-561 ◽  
Author(s):  
Shu Wu ◽  
Jinghong Peng ◽  
Matthew R. Duncan ◽  
Kalyani Kasisomayajula ◽  
Gary Grotendorst ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Embryonic Lung ◽  
Induced Expression ◽  
Alk 5 ◽  
Tgf Β1

scholarly journals Thalidomide inhibits the gene promoter of connective tissue growth factor in human embryonic lung fibroblasts

2020 ◽  
Vol 9 (5) ◽  
pp. 2516-2523
Author(s):  
Yonghui Wu ◽  
Libao Liu ◽  
Jian Zhang ◽  
Lei Huang ◽  
Shaohong Huang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Gene Promoter ◽  
Tissue Growth ◽  
Lung Fibroblasts ◽  
Embryonic Lung ◽  
Human Embryonic Lung

scholarly journals Low-Density Lipoprotein Induced Expression of Connective Tissue Growth Factor via Transactivation of Sphingosine 1-Phosphate Receptors in Mesangial Cells

2012 ◽  
Vol 26 (5) ◽  
pp. 833-845 ◽  
Author(s):  
Hesham M. El-Shewy ◽  
Mimi Sohn ◽  
Parker Wilson ◽  
Mi Hye Lee ◽  
Samar M. Hammad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Pertussis Toxin ◽  
Mesangial Cells ◽  
Tissue Growth ◽  
Low Density ◽  
Induced Expression ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Abstract The pro-fibrotic connective tissue growth factor (CTGF) has been linked to the development and progression of diabetic vascular and renal disease. We recently reported that low-density lipoproteins (LDL) induced expression of CTGF in aortic endothelial cells. However, the molecular mechanisms are not fully defined. Here, we have studied the mechanism by which LDL regulates CTGF expression in renal mesangial cells. In these cells, treatment with pertussis toxin abolished LDL-stimulated activation of ERK1/2 and c-Jun N-terminal kinase (JNK), indicating the involvement of heterotrimeric G proteins in LDL signaling. Treatment with LDL promoted activation and translocation of endogenous sphingosine kinase 1 (SK1) from the cytosol to the plasma membrane concomitant with production of sphingosine-1-phosphate (S1P). Pretreating cells with SK inhibitor, dimethylsphinogsine or down-regulation of SK1 and SK2 revealed that LDL-dependent activation of ERK1/2 and JNK is mediated by SK1. Using a green fluorescent protein-tagged S1P1 receptor as a biological sensor for the generation of physiologically relevant S1P levels, we found that LDL induced S1P receptor activation. Pretreating cells with S1P1/S1P3 receptor antagonist VPC23019 significantly inhibited activation of ERK1/2 and JNK by LDL, suggesting that LDL elicits G protein-dependent activation of ERK1/2 and JNK by stimulating SK1-dependent transactivation of S1P receptors. Furthermore, S1P stimulation induced expression of CTGF in a dose-dependent manner that was markedly inhibited by blocking the ERK1/2 and JNK signaling pathways. LDL-induced CTGF expression was pertussis toxin sensitive and inhibited by dimethylsphinogsine down-regulation of SK1 and VPC23019 treatment. Our data suggest that SK1-dependent S1P receptor transactivation is upstream of ERK1/2 and JNK and that all three steps are required for LDL-regulated expression of CTGF in mesangial cells.

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.

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