Cellular response to transforming growth factor-beta 1 and basic fibroblast growth factor depends on release kinetics and extracellular matrix interactions

被引:89
作者
Dinbergs, ID
Brown, L
Edelman, ER
机构
[1] BRIGHAM & WOMENS HOSP, DEPT MED, DIV CARDIOVASC, BOSTON, MA 02115 USA
[2] HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA
关键词
D O I
10.1074/jbc.271.47.29822
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The extracellular matrix plays an important role in growth factor biology, serving as a potential platform for rapid growth factor mobilization or a sink for concentrated sequestration, We now demonstrate that when a growth factor binds reversibly to the matrix, its effects are augmented by this interaction, and when the factor is absorbed irreversibly to the extracellular matrix, it becomes sequestered. These findings call into question the notion that all growth factors are best presented to cells and tissues in a sustained and controlled fashion, In our studies, we examined basic fibroblast growth factor (bFGF) and transforming growth factor-beta 1 (TGF-beta 1) release kinetics from synthetically fabricated microsphere devices and naturally synthesized extracellular matrix. While the sustained release of bFGF was up to 3.0-fold more potent at increasing vascular endothelial and smooth muscle cell proliferation than bolus administration, the reverse was true for TGF-beta 1 A bolus of TGF-beta 1 inhibited vascular cells up to 3.8-fold more efficiently than the same amount of TGF-beta 1 if control-released. Both growth factors bound to the extracellular matrix, but only bFGF was released in a controlled fashion (2.8%/day). Contact with the extracellular matrix and subsequent release enhanced bFGF activity such that it was 86% more effective at increasing smooth muscle cell numbers than equal amounts of growth factor diluted from frozen stock. TGF-beta 1 remained tightly adherent, The small amount of TGF-beta 1 released from the extracellular matrix was similar to 30% less effective than bolus administration at inhibiting vascular endothelial and smooth muscle cell growth, Sustained growth factor release may be the preferable mode of administration, but only when a similar mode of metabolism is utilized endogenously.
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页码:29822 / 29829
页数:8
相关论文
共 96 条
[61]  
NUGENT MA, 1992, MATER RES SOC SYMP P, V252, P273
[62]   TRANSFORMING GROWTH-FACTOR-BETA TYPE-1 BINDS TO COLLAGEN-IV OF BASEMENT-MEMBRANE MATRIX - IMPLICATIONS FOR DEVELOPMENT [J].
PARALKAR, VM ;
VUKICEVIC, S ;
REDDI, AH .
DEVELOPMENTAL BIOLOGY, 1991, 143 (02) :303-308
[63]   INDUCTION OF RETINAL REGENERATION INVIVO BY GROWTH-FACTORS [J].
PARK, CM ;
HOLLENBERG, MJ .
DEVELOPMENTAL BIOLOGY, 1991, 148 (01) :322-333
[64]   BIPHASIC EFFECT OF TRANSFORMING GROWTH FACTOR-BETA-1 ON INVITRO ANGIOGENESIS [J].
PEPPER, MS ;
VASSALLI, JD ;
ORCI, L ;
MONTESANO, R .
EXPERIMENTAL CELL RESEARCH, 1993, 204 (02) :356-363
[65]   ENHANCED BFGF GENE-EXPRESSION IN RESPONSE TO TRANSFORMING GROWTH-FACTOR-BETA STIMULATION OF AKR-2B CELLS [J].
PERTOVAARA, L ;
SAKSELA, O ;
ALITALO, K .
GROWTH FACTORS, 1993, 9 (01) :81-86
[66]  
PHILLIPS GD, 1990, P SOC EXP BIOL MED, V193, P197
[67]  
PHILLIPS GD, 1993, J SUBMICR CYTOL PATH, V25, P149
[68]   CONTROLLED RELEASE OF NERVE GROWTH-FACTOR FROM A POLYMERIC IMPLANT [J].
POWELL, EM ;
SOBARZO, MR ;
SALTZMAN, WM .
BRAIN RESEARCH, 1990, 515 (1-2) :309-311
[69]   BASIC FIBROBLAST GROWTH-FACTOR REQUIRES A LONG-LASTING ACTIVATION OF PROTEIN-KINASE-C TO INDUCE CELL-PROLIFERATION IN TRANSFORMED FETAL BOVINE AORTIC ENDOTHELIAL-CELLS [J].
PRESTA, M ;
TIBERIO, L ;
RUSNATI, M ;
DELLERA, P ;
RAGNOTTI, G .
CELL REGULATION, 1991, 2 (09) :719-726
[70]   BASIC FIBROBLAST GROWTH-FACTOR IS RELEASED FROM ENDOTHELIAL EXTRACELLULAR-MATRIX IN A BIOLOGICALLY-ACTIVE FORM [J].
PRESTA, M ;
MAIER, JAM ;
RUSNATI, M ;
RAGNOTTI, G .
JOURNAL OF CELLULAR PHYSIOLOGY, 1989, 140 (01) :68-74