Type I collagen can function as a reservoir of basic fibroblast growth factor

Type I collagen can function as a reservoir of basic fibroblast growth factor
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DOI:
10.1016/j.jconrel.2004.07.008
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发表时间:
2004-09-30
影响因子:
10.8
通讯作者:
Tabata, Y
Tabata, Y
中科院分区:
医学1区
文献类型:
--
作者:
Kanematsu, A;Marui, A;Tabata, Y

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细胞外基质(ECM)储存和释放内源性生长因子是控制组织动态平衡和再生的重要生物学事件。碱性成纤维细胞生长因子与硫酸乙酰肝素蛋白多糖之间的相互作用已被广泛研究,并被用作这一系统的原型模型,而I型胶原对碱性成纤维细胞生长因子的低亲和力通常被认为是生物学意义不大的。然而,我们目前的研究发现,在体外和体内生理条件下,碱性成纤维细胞生长因子自发地与I型胶原溶液和海绵相互作用,并被胶原蛋白保护而不受蛋白质降解环境的影响。根据海绵基质的生物降解性,结合在胶原海绵片中的碱性成纤维细胞生长因子在小鼠皮下持续释放,并以剂量依赖的方式显示出局部血管生成活性。肌肉注射胶原微海绵复合碱性成纤维细胞生长因子可显著增加小鼠缺血后肢的血流量,这是单次注射碱性成纤维细胞生长因子所无法达到的。这些结果提示I型胶原作为碱性成纤维细胞生长因子的贮存库的意义和治疗作用。(C)2004爱思唯尔B.V.保留所有权利。
Storage and release of endogenous growth factors by the extracellular matrix (ECM) are important biological events that control tissue homeostasis and regeneration. The interaction between basic fibroblast growth factor (bFGF) and heparan sulfate proteoglycans has been extensively studied and used as a prototype model of such a system, while the lower affinity of fibrillar type I collagen for bFGF has generally been considered biologically insignificant. However, our present investigation revealed that bFGF spontaneously interacts with type I collagen solution and sponges under in vitro and in vivo physiological conditions, and is protected from the proteolytic environment by the collagen. bFGF incorporated in a collagen sponge sheet was sustainedly released in the mouse subcutis according to the biodegradation of the sponge matrix, and exhibited local angiogenic activity in a dose-dependent manner. Intramuscular injection of collagen microsponges incorporating bFGF induced a significant increase in the blood flow in the murine ischemic hindlimb, which could never have been attained by bolus injection of bFGF. These results suggest the significance and therapeutic utility of type I collagen as a reservoir of bFGF. (C) 2004 Elsevier B.V. All rights reserved.