Microarray study reveals a transforming growth factor-β-dependent mechanism of fibrosis in discoid lupus erythematosus

2016 ◽  
Vol 175 (2) ◽  
pp. 302-313 ◽  
Author(s):  
C. Solé ◽  
M. Gimenez-Barcons ◽  
B. Ferrer ◽  
J. Ordi-Ros ◽  
J. Cortés-Hernández
Keyword(s):  
Growth Factor ◽  
Lupus Erythematosus ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Discoid Lupus Erythematosus ◽  
Microarray Study ◽  
Dependent Mechanism

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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