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Connective-Tissue Growth Factor Contributes to TGF-β1–induced Lung Fibrosis
by
Zhou, Quan
, Chong, Sy Giin
, Gholiof, Mahsa
, Tikkanen, Jussi
, Keshavjee, Shaf
, Kolb, Martin R. J.
, Ask, Kjetil
, Lipson, Kenneth E.
, Scallan, Ciaran
, Upagupta, Chandak
, Tsubouchi, Kazuya
, Yanagihara, Toyoshi
in
Animals
/ Antibodies, Monoclonal, Humanized
/ Cellular biology
/ Connective tissue
/ Connective tissue growth factor
/ Connective Tissue Growth Factor - genetics
/ Endothelial cells
/ Endothelial Cells - metabolism
/ Fibroblasts
/ Fibrosis
/ Growth factors
/ Idiopathic Pulmonary Fibrosis - genetics
/ Lung diseases
/ Medical research
/ Phenotypes
/ Pulmonary fibrosis
/ Rats
/ Smooth muscle
/ Transforming Growth Factor beta1 - pharmacology
/ Transforming growth factor-b
/ Transforming growth factor-b1
2022
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Connective-Tissue Growth Factor Contributes to TGF-β1–induced Lung Fibrosis
by
Zhou, Quan
, Chong, Sy Giin
, Gholiof, Mahsa
, Tikkanen, Jussi
, Keshavjee, Shaf
, Kolb, Martin R. J.
, Ask, Kjetil
, Lipson, Kenneth E.
, Scallan, Ciaran
, Upagupta, Chandak
, Tsubouchi, Kazuya
, Yanagihara, Toyoshi
in
Animals
/ Antibodies, Monoclonal, Humanized
/ Cellular biology
/ Connective tissue
/ Connective tissue growth factor
/ Connective Tissue Growth Factor - genetics
/ Endothelial cells
/ Endothelial Cells - metabolism
/ Fibroblasts
/ Fibrosis
/ Growth factors
/ Idiopathic Pulmonary Fibrosis - genetics
/ Lung diseases
/ Medical research
/ Phenotypes
/ Pulmonary fibrosis
/ Rats
/ Smooth muscle
/ Transforming Growth Factor beta1 - pharmacology
/ Transforming growth factor-b
/ Transforming growth factor-b1
2022
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Connective-Tissue Growth Factor Contributes to TGF-β1–induced Lung Fibrosis
by
Zhou, Quan
, Chong, Sy Giin
, Gholiof, Mahsa
, Tikkanen, Jussi
, Keshavjee, Shaf
, Kolb, Martin R. J.
, Ask, Kjetil
, Lipson, Kenneth E.
, Scallan, Ciaran
, Upagupta, Chandak
, Tsubouchi, Kazuya
, Yanagihara, Toyoshi
in
Animals
/ Antibodies, Monoclonal, Humanized
/ Cellular biology
/ Connective tissue
/ Connective tissue growth factor
/ Connective Tissue Growth Factor - genetics
/ Endothelial cells
/ Endothelial Cells - metabolism
/ Fibroblasts
/ Fibrosis
/ Growth factors
/ Idiopathic Pulmonary Fibrosis - genetics
/ Lung diseases
/ Medical research
/ Phenotypes
/ Pulmonary fibrosis
/ Rats
/ Smooth muscle
/ Transforming Growth Factor beta1 - pharmacology
/ Transforming growth factor-b
/ Transforming growth factor-b1
2022
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Connective-Tissue Growth Factor Contributes to TGF-β1–induced Lung Fibrosis
Journal Article
Connective-Tissue Growth Factor Contributes to TGF-β1–induced Lung Fibrosis
2022
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Overview
Idiopathic pulmonary fibrosis is a fatal lung disease characterized by progressive and excessive accumulation of myofibroblasts and in the lung. Connective-tissue growth factor (CTGF) exacerbates pulmonary fibrosis in radiation-induced lung fibrosis, and in this study, we demonstrate upregulation of CTGF in a rat lung fibrosis model induced by an adenovirus vector encoding active TGF-β1 (AdTGF-β1). We show that CTGF is also upregulated in patients with idiopathic pulmonary fibrosis. Expression of CTGF was upregulated in vascular smooth muscle cells cultured from fibrotic lungs on Days 7 and 14 as well as endothelial cells sorted from fibrotic lungs on Days 14 and 28. These findings suggest contributions of different cells in maintaining the fibrotic phenotype during fibrogenesis. Treatment of fibroblasts with recombinant CTGF along with TGF-β increases profibrotic markers in fibroblasts, confirming the synergistic effect of recombinant CTGF with TGF-β in inducing pulmonary fibrosis. Also, the fibrotic extracellular matrix upregulated CTGF expression, compared with the 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 treatment of pulmonary fibrosis.
Publisher
Oxford University Press
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