Connective tissue growth factor siRNA modulates mRNA levels for a subset of molecules in normal and TGF-?1?stimulated porcine skin fibroblasts

2004 ◽  
Vol 12 (2) ◽  
pp. 205-216 ◽  
Author(s):  
Jian Fei Wang ◽  
Merle E. Olson ◽  
Lingling Ma ◽  
David R. Brigstock ◽  
David A. Hart
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Skin Fibroblasts ◽  
Mrna Levels ◽  
Porcine Skin

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.

Abstract P224: Connective Tissue Growth Factor Plays a Key Role in Myocardial Fibrosis After Angiotensin II Exposure

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Nicole L Rosin ◽  
Jean-François Légaré ◽  
Timothy D Lee
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Tissue Growth ◽  
Mrna Levels

Background: AngiotensinII (AngII) exposure to rodents is a common model of fibrosis, characterized by hypertension, hypertrophy and eventual deposition of excess extracellular matrix (ECM) proteins resulting in organ dysfunction. We have previously shown that cellular infiltration of bone marrow derived progenitor cells (fibrocytes) occurs prior to ECM deposition and is associated with production of the connective tissue growth factor (CTGF) and transforming growth factor beta (TGF-β). The objective of this project was to characterize the role of CTGF in promoting fibrocyte recruitment and subsequent fibrosis after AngII exposure. Methods: Mice were treated with AngII or saline using an osmotic mini-pump at 2.8mg/kg/day. After 6hr to 7d hearts were excised and embedded in paraffin or prepared for mRNA isolation. Immunohistochemistry was used to determine extent and localization of CTGF protein. Quantitative RT-PCR was used to determine relative CTGF and TGF-β mRNA levels. Primary cardiomyocyte and fibrocyte cultures were isolated from neonatal or 3d AngII exposed animals respectively. Primary cultures were stimulated to determine the source (qRT-PCR) and function (proliferation, migration and differentiation) of CTGF. Results: In animals exposed to AngII, CTGF mRNA peaked the earliest at 6hr (21-fold; p<0.01) when compared to TGFbeta, which peaked at 3d (5-fold; p<0.05). Concurrent CTGF protein expression was evident by 3d of AngII exposure and appeared localized to the cardiomyocytes. Findings were confirmed using isolated cardiomyocytes, which significantly increased expression of CTGF in response to AngII (2-fold; p<0.05). While CTGF did not promote fibrocyte migration in transwell chamber assay it promoted significant fibrocyte proliferation in vitro (2-fold; p<0.05). Conclusion: We provide strong evidence that AngII exposure first results in the production of CTGF by cardiomyocytes. Furthermore, we have shown that CTGF does not promote migration as a chemokine but instead contributes to proliferation of fibrocytes once recruited from the bone marrow into the myocardium.

Recombinant connective tissue growth factor modulates porcine skin fibroblast gene expression

2003 ◽  
Vol 11 (3) ◽  
pp. 220-229 ◽  
Author(s):  
Jian Fei Wang ◽  
Merle E. Olson ◽  
Deanna K. Ball ◽  
David R. Brigstock ◽  
David A. Hart
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Skin Fibroblast ◽  
Tissue Growth ◽  
Porcine Skin
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