scholarly journals Direct Thrombin Inhibition Reduces Lung Collagen, Accumulation, and Connective Tissue Growth Factor mRNA Levels in Bleomycin-Induced Pulmonary Fibrosis

2001 ◽  
Vol 159 (4) ◽  
pp. 1383-1395 ◽  
Author(s):  
David C.J. Howell ◽  
Neil R. Goldsack ◽  
Richard P. Marshall ◽  
Robin J. McAnulty ◽  
Richard Starke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Thrombin Inhibition ◽  
Collagen Accumulation

Elevated expression of connective tissue growth factor, osteopontin and increased collagen content in human ascending thoracic aortic aneurysms

Vascular ◽  
2013 ◽  
Vol 22 (1) ◽  
pp. 20-27 ◽  
Author(s):  
YH Meng ◽  
C Tian ◽  
L Liu ◽  
L Wang ◽  
Q Chang
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Aortic Aneurysms ◽  
Collagen Content ◽  
Control Group ◽  
Mrna Levels ◽  
Thoracic Aortic Aneurysms ◽  
Protein Levels

Little is known about the molecular mechanisms of ascending thoracic aortic aneurysms (ATAAs). Abnormal extracellular matrix changes and variations of vascular smooth muscle cells (VSMCs) have been implicated in abdominal aortic aneurysm formation. Our objective was to investigate the alterations of collagen, stimulators of collagen synthesis and synthetic VSMCs in patients with ATAA. Surgical samples from ATAA were taken from 20 patients, and 18 control aortas were obtained during coronary artery bypass surgery. All aortic wall specimens were fixed for histology and immunohistochemistry for collagen, connective tissue growth factor (CTGF) and osteopontin. Realtime polymerase chain reaction was used to determine their mRNA expression. Histology and semi-quantitative analysis demonstrated that protein levels of collagen, CTGF and osteopontin significantly increased by 1.9-, 1.4- and 2.2-fold, respectively ( P < 0.01 for all) in the ATAA group than in the control group. Similar results were shown in mRNA levels of type Iα1and IIIα1 collagen, CTGF and osteopontin. The protein levels of CTGF and osteopontin were positively correlated with aortic diameter ( r = 0.67, r = 0.73; P < 0.01 for both). In conclusion, overexpression of aortic CTGF and synthetic VSMCs marker (osteopontin), which is likely to be responsible for elevated aortic collagen content, may provide a potential mechanism for aneurysmal enlargement.

scholarly journals Skeletal Overexpression of Connective Tissue Growth Factor Impairs Bone Formation and Causes Osteopenia

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4374-4381 ◽  
Author(s):  
Anna Smerdel-Ramoya ◽  
Stefano Zanotti ◽  
Lisa Stadmeyer ◽  
Deena Durant ◽  
Ernesto Canalis
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Bone Formation ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Bmp Signaling ◽  
Mrna Levels ◽  
Mineral Density ◽  
Ccn Family ◽  
Igf I

Connective tissue growth factor (CTGF), a member of the CCN family of proteins, is expressed in skeletal cells, and the ctgf null mutation leads to neonatal lethality due to defects in skeletal development. To define the function of CTGF in the postnatal skeleton, we created transgenic mice overexpressing CTGF under the control of the human osteocalcin promoter. CTGF transgenic female and male mice exhibited a significant decrease in bone mineral density, compared with wild-type littermate controls. Bone histomorphometry revealed that CTGF overexpression caused decreased trabecular bone volume due to impaired osteoblastic activity because mineral apposition and bone formation rates were decreased. Osteoblast and osteoclast number and bone resorption were not altered. Calvarial osteoblasts and stromal cells from CTGF transgenics displayed decreased alkaline phosphatase and osteocalcin mRNA levels and reduced bone morphogenetic protein (BMP) signaling mothers against decapentaplegic, Wnt/β-catenin, and IGF-I/Akt signaling. In conclusion, CTGF overexpression in vivo causes osteopenia, secondary to decreased bone formation, possibly by antagonizing BMP, Wnt, and IGF-I signaling and activity.

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 FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary fibrosis

2016 ◽  
Vol 47 (5) ◽  
pp. 1481-1491 ◽  
Author(s):  
Ganesh Raghu ◽  
Mary Beth Scholand ◽  
João de Andrade ◽  
Lisa Lancaster ◽  
Yolanda Mageto ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Monoclonal Antibody ◽  
Growth Factor ◽  
Idiopathic Pulmonary Fibrosis ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Open Label

FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis.This open-label phase 2 trial evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks.FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function.Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway.

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