scholarly journals Anaplastic lymphoma kinase 5 (ALK5; TGFBR1); membrane type 1 matrix metalloproteinase (MT1-MMP; MMP14); small mothers against decapentaplegic homolog 3 (SMAD3); prostaglandin E2 receptor (PGE2, PTGER2); transforming growth factor-β1 (TGF-β1)

2008 ◽  
Vol 1 (23) ◽  
pp. 563-563
Keyword(s):  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Anaplastic Lymphoma Kinase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Anaplastic Lymphoma ◽  
Membrane Type ◽  
Prostaglandin E2 Receptor ◽  
Tgf Β1

Transforming growth factor-β1 induces cerebrovascular dysfunction and astrogliosis through angiotensin II type 1 receptor-mediated signaling pathways

2018 ◽  
Vol 96 (5) ◽  
pp. 527-534 ◽  
Author(s):  
Brice Ongali ◽  
Nektaria Nicolakakis ◽  
Xin-Kang Tong ◽  
Clotilde Lecrux ◽  
Hans Imboden ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Cerebrovascular Reactivity ◽  
Cerebrovascular Dysfunction ◽  
Tgf Β1

Transgenic mice constitutively overexpressing the cytokine transforming growth factor-β1 (TGF-β1) (TGF mice) display cerebrovascular alterations as seen in Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID), but no or only subtle cognitive deficits. TGF-β1 may exert part of its deleterious effects through interactions with angiotensin II (AngII) type 1 receptor (AT1R) signaling pathways. We test such interactions in the brain and cerebral vessels of TGF mice by measuring cerebrovascular reactivity, levels of protein markers of vascular fibrosis, nitric oxide synthase activity, astrogliosis, and mnemonic performance in mice treated (6 months) with the AT1R blocker losartan (10 mg/kg per day) or the angiotensin converting enzyme inhibitor enalapril (3 mg/kg per day). Both treatments restored the severely impaired cerebrovascular reactivity to acetylcholine, calcitonin gene-related peptide, endothelin-1, and the baseline availability of nitric oxide in aged TGF mice. Losartan, but not enalapril, significantly reduced astrogliosis and cerebrovascular levels of profibrotic protein connective tissue growth factor while raising levels of antifibrotic enzyme matrix metallopeptidase-9. Memory was unaffected by aging and treatments. The results suggest a pivotal role for AngII in TGF-β1-induced cerebrovascular dysfunction and neuroinflammation through AT1R-mediated mechanisms. Further, they suggest that AngII blockers could be appropriate against vasculopathies and astrogliosis associated with AD and VCID.

scholarly journals Thrombospondin 1 does not activate transforming growth factor β1 in a chemically defined system or in smooth-muscle-cell cultures

2000 ◽  
Vol 350 (1) ◽  
pp. 291-298 ◽  
Author(s):  
David J. GRAINGER ◽  
Emma K. FROW
Keyword(s):  
Cell Culture ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Smooth Muscle Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Matrix Metalloproteinase 2 ◽  
Tgf Β1

The cytokine transforming growth factor β1 (TGF-β1) is secreted in a latent form that has no known biological activity. The conversion of latent TGF-β1 into its biologically active 25kDa form is thought to be an important step in the regulation of TGF-β activity both in cell culture and in vivo. Thrombospondin (TSP)-1, a 360kDa platelet α-granule and extracellular matrix protein, has been shown to participate in TGF-β1 activation. We have used a chemically defined system to examine the mechanism of TSP-1-mediated TGF-β1 activation. However, the addition of two different preparations of TSP-1 to recombinant small latent TGF-β1 in the test tube resulted in only a very small increase in the proportion of the TGF-β1 able to bind to the TGF-β type II receptor: from 0.1% to a maximum of 0.4%. This small effect was not specific for TSP-1: matrix metalloproteinase 2, tissue inhibitor of matrix metalloproteinase 2 and active plasminogen activator inhibitor 1, but not transglutaminase, human serum albumin or immunoglobulin, had quantitatively similar effects on latent TGF-β1. Furthermore, no change in the activity associated with small latent TGF-β1 was noted in either mink lung epithelial cell or rat aortic smooth-muscle cell culture systems in the presence of TSP-1 (or TSP-1-derived peptides). We conclude that TSP-1, either alone or in the presence of cultured smooth-muscle cells (a cell type known to activate latent TGF-β in vitro and in vivo) is unable to activate latent TGF-β1. Any TSP-mediated activation of TGF-β1 must depend on additional factor(s) not present in our systems.

Regulation of human mesangial cell collagen expression by transforming growth factor-β1

1998 ◽  
Vol 275 (3) ◽  
pp. F458-F466 ◽  
Author(s):  
Anne-Christine Poncelet ◽  
H. William Schnaper
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β1 ◽  
Collagen Turnover ◽  
Collagen Mrna ◽  
Collagen Expression ◽  
Membrane Type ◽  
Tgf Β1

Transforming growth factor (TGF)-β1 has been implicated in glomerular extracellular matrix accumulation. Since the spectrum and mechanism of changes in collagen turnover have not been fully characterized, we evaluated effects of TGF-β1 on collagen expression by human mesangial cells. TGF-β1 induced increased α1(I), α1(III), and α1(IV) collagen mRNA expression. Greater mRNA expression of matrix metalloproteinase (MMP)-2 was compensated by increased tissue inhibitor of metalloproteinases (TIMP)-2 mRNA. There was no change in TIMP-1 or membrane-type MMP mRNA expression, whereas MMP-1 mRNA decreased. Types I and IV collagen protein accumulated in both the cell layer and medium. Changes in collagen mRNA and protein occurred within 4 and 8 h, respectively. MMP-2 and TIMP-1 and -2 activities showed little change. Cycloheximide markedly decreased collagen detection within 4 h and reversed late, but not early, changes in α1(I) collagen mRNA. In this system, increased synthesis may be more significant than degradation for collagen accumulation, but collagen is short-lived in culture. Diverse TGF-β1 actions on collagen turnover may be either immediate or mediated through synthesis of regulatory molecules.

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