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Titolo:
Heparan sulfate mediates bFGF transport through basement membrane by diffusion with rapid reversible binding
Autore:
Dowd, CJ; Cooney, CL; Nugent, MA;
Indirizzi:
Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA Boston Univ Boston MA USA 02118 h Med, Dept Biochem, Boston, MA 02118 USA Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA Boston Univ Boston MA USA 02118 ed, Dept Ophthalmol, Boston, MA 02118 USA MIT, Dept Chem Engn, Cambridge, MA 02139 USA MIT Cambridge MA USA 02139MIT, Dept Chem Engn, Cambridge, MA 02139 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 8, volume: 274, anno: 1999,
pagine: 5236 - 5244
SICI:
0021-9258(19990219)274:8<5236:HSMBTT>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROBLAST GROWTH-FACTOR; SUBENDOTHELIAL EXTRACELLULAR-MATRIX; BOVINE DESCEMETS MEMBRANE; PLASMINOGEN-ACTIVATOR PRODUCTION; ENDOTHELIAL-CELLS; PROTEOLYTIC DEGRADATION; CORNEAL ENDOTHELIUM; MAGNETIC-RESONANCE; ANGIOGENIC PROTEIN; BALB/C3T3 CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
53
Recensione:
Indirizzi per estratti:
Indirizzo: Nugent, MA Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA BostonUniv Boston MA USA 02118 Biochem, Boston, MA 02118 USA
Citazione:
C.J. Dowd et al., "Heparan sulfate mediates bFGF transport through basement membrane by diffusion with rapid reversible binding", J BIOL CHEM, 274(8), 1999, pp. 5236-5244

Abstract

Basic fibroblast growth factor (bFGF) is a pluripotent cytokine with a wide range of target cells. Heparan sulfate binds bFGF, and this interaction has been demonstrated to protect bFGF against physical denaturation and protease degradation. The high concentrations of heparan sulfate in basement membranes have implicated these matrices as storage sites for bFGF in vivo. However, the mechanisms by which basement membranes modulate bFGF storage and release is unknown. To gain insight into these mechanisms, we have developed experimental and mathematical models of extracellular growth factor transport through basement membrane. Intact Descemet's membranes isolated frombovine corneas were mounted within customized diffusion cells and growth factor transport was measured under a variety of conditions that decoupled the diffusion process from the heparan sulfate binding phenomenon. Transportexperiments were conducted with bFGF and interleukin 1 beta. In addition, bFGF-heparan sulfate binding was disrupted in diffusion studies with high ionic strength buffer and buffers containing protamine sulfate. Transport ofbFGF was enhanced dramatically when heparan sulfate binding was inhibited. This process was modeled as a problem of diffusion with fast reversible binding. Experimental parameters were incorporated into a mathematical model and independent simulations were run that showed that the experimental datawere accurately predicted by the mathematical model. Thus, this study indicated that basement membranes function as dynamic regulators of growth factor transport, allowing for rapid response to changing environmental conditions. The fundamental principles controlling bFGF transport through basementmembrane that have been identified here might have applications in understanding how growth factor distribution is regulated throughout an organism during development and in the adult state.

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Documento generato il 04/12/20 alle ore 16:12:35