Fibroblast growth factors

Baird, Andrew; Walicke, Patricia A.

doi:10.1093/oxfordjournals.bmb.a072333

Cited by 195 publications

(66 citation statements)

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“…Basic fibroblast growth factor (bFGF) 1 is a pluripotent growth factor that affects a wide range of cell types of mesodermal, endodermal, and ectodermal origin. It has been implicated in processes ranging from wound healing to tumor growth (1,2).…”

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confidence: 99%

“…It has been implicated in processes ranging from wound healing to tumor growth (1,2). Like the other members of the FGF family, bFGF binds heparin and heparan sulfate (HS).…”

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confidence: 99%

“…: 617-638-4169; Fax: 617-638-5337; E-mail: nugent@med-biochem.bu.edu. 1 The abbreviations used are: bFGF, basic fibroblast growth factor; HS, heparan sulfate; ECM, extracellular matrix; DM, Descemet's membrane; BSA, bovine serum albumin; PBS, phosphate-buffered saline; IL-1␤, interleukin 1␤. cultured cell layers.…”

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Heparan Sulfate Mediates bFGF Transport through Basement Membrane by Diffusion with Rapid Reversible Binding

Dowd

Cooney

Nugent

1999

Journal of Biological Chemistry

154

141

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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 from bovine 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. Transport experiments were conducted with bFGF and interleukin 1␤. In addition, bFGF-heparan sulfate binding was disrupted in diffusion studies with high ionic strength buffer and buffers containing protamine sulfate. Transport of bFGF 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 data were 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 basement membrane 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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confidence: 99%

“…It has been implicated in processes ranging from wound healing to tumor growth (1,2). Like the other members of the FGF family, bFGF binds heparin and heparan sulfate (HS).…”

mentioning

confidence: 99%

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Heparan Sulfate Mediates bFGF Transport through Basement Membrane by Diffusion with Rapid Reversible Binding

Dowd

Cooney

Nugent

1999

Journal of Biological Chemistry

154

141

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“…These results suggest that the ECM HSPG provide a natural storage depot for bFGF and possibly other growth-promoting factors. Displacement of bFGF from its storage within basement membranes and ECM may provide a novel mechanism for induction of neovascularization in normal and pathological situations (Baird and Walicke, 1989;Vlodavsky et al, 1990). Such a role can be ascribed to an endo-f3-D-glucuronidase (heparanase) that degrades HS side chains in the subendothelial ECM (Vlodavsky et al, 1983;Nakajima et al, 1988).…”

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confidence: 99%

Heparanase activity expressed by platelets, neutrophils, and lymphoma cells releases active fibroblast growth factor from extracellular matrix.

1990

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Incubation of platelets, neutrophils, and lymphoma cells with Descemet's membranes of bovine corneas and with the extracellular matrix (ECM) produced by cultured corneal endothelial cells resulted in release of basic fibroblast growth factor (bFGF), which stimulated the proliferation of 3T3 fibroblasts and vascular endothelial cells. Similar requirements were observed for release of endogenous bFGF stored in Descemet's membrane and of exogenous bFGF sequestered by the subendothelial ECM. Release of ECM-resident bFGF by platelets, neutrophils, and lymphoma cells was inhibited by carrageenan lambda, but not by protease inhibitors, in correlation with the inhibition of heparanase activity expressed by these cells. Degradation of the ECM-heparan sulfate side chains by this endo-beta-D-glucuronidase is thought to play an important role in cell invasion, particularly in the extravasation of blood-borne tumor cells and activated cells of the immune system. We propose that both heparanase and ECM-resident bFGF may modulate the cell response to contact with its local environment. Heparanase-mediated release of active bFGF from storage in basement membranes provides a novel mechanism for a localized induction of neovascularization in various normal and pathological processes, such as wound healing, inflammation, and tumor development.

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“…They were the first mem bers of a novel class of mitogens with a strong affinity for heparin to be isolated. Since their discovery, six members of the larger family have been isolated and characterised from a wide variety of sources and exhibit pleiotropic effects on a broad range of cell types and also act as media tors of developmental pathways in different biological sys tems [1,2], The range of properties shown by the FGF family suggests that these might be important molecules in the processes of embryonic development. The factors may modulate the rate of expansion of stem cell populations by regulating the differentiation programmes.…”

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confidence: 99%