Interleukin-1β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism

2002 ◽  
Vol 140 (5) ◽  
pp. 342-350 ◽  
Author(s):  
David A. Vesey ◽  
Catherine Cheung ◽  
Leila Cuttle ◽  
Zoltan Endre ◽  
Glenda Gobe ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Production ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 1Β ◽  
Fibroblast Proliferation ◽  
Dependent Mechanism

scholarly journals Identification of the growth factor–binding sequence in the extracellular matrix protein MAGP-1

2020 ◽  
Vol 295 (9) ◽  
pp. 2687-2697 ◽  
Author(s):  
Thomas J. Broekelmann ◽  
Nicholas K. Bodmer ◽  
Robert P. Mecham
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Extracellular Matrix Protein ◽  
Surface Plasmon Resonance Analysis ◽  
Factor Binding

Microfibril-associated glycoprotein-1 (MAGP-1) is a component of vertebrate extracellular matrix (ECM) microfibrils that, together with the fibrillins, contributes to microfibril function. Many of the phenotypes associated with MAGP-1 gene inactivation are consistent with dysregulation of the transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling system. We have previously shown that full-length MAGP-1 binds active TGFβ-1 and some BMPs. The work presented here further defines the growth factor–binding domain of MAGP-1. Using recombinant domains and synthetic peptides, along with surface plasmon resonance analysis to measure the kinetics of the MAGP-1–TGFβ-1 interaction, we localized the TGFβ- and BMP-binding site in MAGP-1 to a 19-amino acid–long, highly acidic sequence near the N terminus. This domain was specific for binding active, but not latent, TGFβ-1. Growth factor activity experiments revealed that TGFβ-1 retains signaling activity when complexed with MAGP-1. Furthermore, when bound to fibrillin, MAGP-1 retained the ability to interact with TGFβ-1, and active TGFβ-1 did not bind fibrillin in the absence of MAGP-1. The absence of MAGP was sufficient to raise the amount of total TGFβ stored in the ECM of cultured cells, suggesting that the MAGPs compete with the TGFβ large latent complex for binding to microfibrils. Together, these results indicate that MAGP-1 plays an active role in TGFβ signaling in the ECM.

The effect of interleukin-1β and transforming growth factor β on cathepsin B activity in human articular chondrocytes

1994 ◽  
Vol 41 (S2) ◽  
pp. C198-C200 ◽  
Author(s):  
M. H. M. Meijers ◽  
C. M. Aisa ◽  
M. E. J. Billingham ◽  
R. G. G. Russell ◽  
R. A. D. Bunning
Keyword(s):  
Growth Factor ◽  
Cathepsin B ◽  
Transforming Growth Factor ◽  
Articular Chondrocytes ◽  
Transforming Growth Factor Β ◽  
Interleukin 1Β ◽  
Human Articular Chondrocytes

scholarly journals Transforming Growth Factor β Depletion Is the Primary Determinant of Smad Signaling Kinetics

2009 ◽  
Vol 29 (9) ◽  
pp. 2443-2455 ◽  
Author(s):  
David C. Clarke ◽  
Meredith L. Brown ◽  
Richard A. Erickson ◽  
Yigong Shi ◽  
Xuedong Liu
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Ligand Concentration ◽  
Type Ii ◽  
Reversible Binding ◽  
Primary Determinant ◽  
Ligand Depletion ◽  
Dependent Mechanism

ABSTRACT A cell's decision to growth arrest, apoptose, or differentiate in response to transforming growth factor β (TGF-β) superfamily ligands depends on the ligand concentration. How cells sense the concentration of extracellular bioavailable TGF-β remains poorly understood. We therefore undertook a systematic quantitative analysis of how TGF-β ligand concentration is transduced into downstream phospho-Smad2 kinetics, and we found that the rate of TGF-β ligand depletion is the principal determinant of Smad signal duration. TGF-β depletion is caused by two mechanisms: (i) cellular uptake of TGF-β by a TGF-β type II receptor-dependent mechanism and (ii) reversible binding of TGF-β to the cell surface. Our results indicate that cells sense TGF-β dose by depleting TGF-β via constitutive TGF-β type II receptor trafficking processes. Our results also have implications for the role of the TGF-β type II receptor in disease, as tumor cells harboring TGF-β type II receptor mutations exhibit impaired TGF-β depletion, which may contribute to the overproduction of TGF-β and a consequently poor prognosis in cancer.

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