Cellular Response to Transforming Growth Factor-β1 and Basic Fibroblast Growth Factor Depends on Release Kinetics and Extracellular Matrix Interactions*
Cellular Response to Transforming Growth Factor-β1 and Basic Fibroblast Growth Factor Depends on Release Kinetics and Extracellular Matrix Interactions*
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细胞对转化生长因子-β1 和碱性成纤维细胞生长因子的反应取决于释放动力学和细胞外基质相互作用*
DOI：
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发表时间：
1996
影响因子：
4.8
通讯作者：
E. Edelman
中科院分区：
文献类型：
--
作者：
I. D. Dinbergs;L. Brown;E. Edelman
细胞外基质在生长因子生物学中起着重要的作用，可以作为生长因子快速动员的潜在平台或集中隔离的水槽。我们现在证明，当一个生长因子可逆地结合到基质，它的影响是由这种相互作用增强，当该因子被不可逆地吸收到细胞外基质，它成为隔离。这些发现对所有生长因子最好以持续和受控的方式呈现给细胞和组织的概念提出了质疑。在我们的研究中，我们检查了合成制造的微球装置和天然合成的细胞外基质中碱性成纤维细胞生长因子（bFGF）和转化生长因子-β1（TGF-β1）的释放动力学。虽然bFGF的持续释放在增加血管内皮细胞和平滑肌细胞增殖方面的效力比推注给药高3.0倍，但TGF-β1的情况正好相反。一团TGF-β1对血管细胞的抑制作用比相同量的TGF-β1（如果控制释放）高3.8倍。两种生长因子都与细胞外基质结合，但只有bFGF以受控方式释放（2.8%/天）。与细胞外基质的接触和随后的释放增强了bFGF的活性，使得它在增加平滑肌细胞数量方面比等量的从冷冻原液稀释的生长因子有效86%。TGF-β1保持紧密粘附。从细胞外基质释放的少量TGF-β1在抑制血管内皮细胞和平滑肌细胞生长方面的效果比推注给药低约30%。持续的生长因子释放可能是优选的给药模式，但仅当内源性利用类似的代谢模式时。
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-β1 (TGF-β1) 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-β1. A bolus of TGF-β1 inhibited vascular cells up to 3.8-fold more efficiently than the same amount of TGF-β1 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-β1 remained tightly adherent. The small amount of TGF-β1 released from the extracellular matrix was ∼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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DOI：
10.1073/pnas.90.4.1513
发表时间：
1993-02-15
影响因子：
11.1
作者：
EDELMAN, ER;NUGENT, MA;KARNOVSKY, MJ
通讯作者：
KARNOVSKY, MJ
DOI：
10.1172/jci117627
发表时间：
1995
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Gou Young Koh;Seong-Jin Kim;M. Klug;K. Park;K. Park;M. Soonpaa;Loren J. Field
通讯作者：
Gou Young Koh;Seong-Jin Kim;M. Klug;K. Park;K. Park;M. Soonpaa;Loren J. Field
转化生长因子 beta 1 刺激 Balb/c3T3 细胞中碱性成纤维细胞生长因子结合蛋白聚糖的产生。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Nugent,MA;Edelman,ER
通讯作者：
Edelman,ER
BALB/c 3T3 细胞中 DNA 合成需要长期生长因子暴露和差异酪氨酸磷酸化。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Zhan,X;Hu,X;Friesel,R;Maciag,T
通讯作者：
Maciag,T
DOI：
10.1073/pnas.87.10.3773
发表时间：
1990-05-01
影响因子：
11.1
作者：
EDELMAN, ER;ADAMS, DH;KARNOVSKY, MJ
通讯作者：
KARNOVSKY, MJ