R136K fibroblast growth factor-1 mutant induces heparin-independent migration of endothelial cells through fibrin glue

Erzurum, Victor Z.; Bian, Jiefang; Husak, Vicki; Ellinger, Joan; Li, Xue; Burgess, Wilson H.; Greisler, Howard P.

doi:10.1067/mva.2003.177

Cited by 27 publications

(16 citation statements)

References 14 publications

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“…[33] In another study by the same group, the dose effect of the non-glycosylated BMP-2 was found with significant differences between 2 and 5 μg of non-glycosylated BMP-2 but no such difference between 5 and 10 μg. [34] Modification of factors can extend beyond affecting solubility, as shown in two studies by Erzurum et al[35] and Shireman et al[36], where two different mutations of FGF-1 reduce the susceptibility of the growth factor to cleavage by thrombin and thus extend its duration of bioactivity. This is especially important in drug delivery utilizing fibrin glue due to the high levels of thrombin used to form the gel.…”

Section: Loaded Factor Drug and Vector Systemsmentioning

confidence: 99%

Fibrin glue as a drug delivery system

Spicer

Mikos

2010

Journal of Controlled Release

161

107

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Fibrin glue has been used surgically for decades for hemostasis as well as a sealant. It has also been researched as both a gel for cell delivery and a vehicle for drug delivery. The drug delivery applications for fibrin glue span tissue engineering to chemotherapy and involve several mechanisms for drug matrix interactions and control of release kinetics. Additionally, drugs or factors can be loaded in the gel via impregnation and tethering to the gel through covalent linkages or affinity based systems. This review highlights recent research of fibrin glue as a drug delivery vehicle.

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Section: Loaded Factor Drug and Vector Systemsmentioning

confidence: 99%

Fibrin glue as a drug delivery system

Spicer

Mikos

2010

Journal of Controlled Release

161

107

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“…R136K and R136K-CBD was constructed as described in our previous published protocols [16] [17]. In brief, R136K was generated using MORPH Site-Specific Plasmid DNA Mutagenesis Kit (5 Prime–3 Prime, Inc., Boulder, Co).…”

Section: Local Delivery Of a Collagen Binding Fgf-1 Chimera To Smoothmentioning

confidence: 99%

Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering

et al. 2010

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We investigated the delivery of R136K-CBD (a collagen binding mutuat chimera of fibroblast growth factor-1) with a type I collagen scaffold as the delivery vehicle to smooth muscle cells (SMCs) for vascular tissue engineering. The binding affinity of R136K-CBD to 3-D collagen scaffolds was investigated both in the presence and absence of cells and/or salts. 2-D and 3-D visualization of delivery of R136K-CBD into SMCs was accomplished by combined fluorescent and reflection confocal microscopy. The mitogenic effect of collagen-immobilized R136K-CBD on SMCs in 3-D collagen was studied by Cyquant assay at different time intervals. In the group devoid of salt and cells, no detectable release of R136K-CBD into overlying culture media was found, compared with burst-and-continuous release of R136K and FGF-1 over a 14-day period in all other groups. The release rate of R136K-CBD was 1.7 and 1.6 fold less than R-136K and FGF-1 when media was supplemented with 2M salt (P<0.0001), and 2.6 and 2.5 fold less in cell-populated collagen hydrogels (P<0.0001), respectively. R136K-CBD showed essentially uniform binding to collagen and its distribution was dependent on that of the collagen scaffold. Internalization of R136K-CBD into SMCs was documented by confocal microscopy. 3-D local delivery of collagen-immobilized R136K-CBD increased the proliferation of SMCs in the collagen matrix to significantly greater levels and for a significantly greater duration than R136K or FGF-1, with 2.0 and 2.1 fold more mitogenicity than R136K and FGF-1 respectively (P<0.0001) at day 7. The results suggest that our collagen binding fusion protein is an effective strategy for growth factor delivery for vascular tissue engineering.

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“…Thrombin can cleave FGF1; however, proteolytic cleavage of extracellular FGF1 can be prevented by its binding to heparan sulfate proteoglycans of the cell surface (Rosengart et al, 1988). Thus, for better detection of FGF1 released into the medium, we are using in our experiments the thrombin uncleavable FGF1R136K mutant (Erzurum et al, 2003;Duarte et al, 2006). Both vector control and sJ1 39-kDa transfectants exported FGF1 in response to temperature stress (42°C), whereas FGF1 release under nonstress conditions (37°C) was only observed in the sJ1 39-kDa NIH 3T3 transfectants ( Figure 3B).…”

Section: Sj1 39 Kda Induces Fgf1 Expression and Releasementioning

confidence: 99%

Novel Cross-Talk between Three Cardiovascular Regulators: Thrombin Cleavage Fragment of Jagged1 Induces Fibroblast Growth Factor 1 Expression and Release

Duarte

Kolev

Kacer

et al. 2008

MBoC

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Angiogenesis is controlled by several regulatory mechanisms, including the Notch and fibroblast growth factor (FGF) signaling pathways. FGF1, a prototype member of FGF family, lacks a signal peptide and is released through an endoplasmic reticulum-Golgi-independent mechanism. A soluble extracellular domain of the Notch ligand Jagged1 (sJ1) inhibits Notch signaling and induces FGF1 release. Thrombin, a key protease of the blood coagulation cascade and a potent inducer of angiogenesis, stimulates rapid FGF1 release through a mechanism dependent on the major thrombin receptor protease-activated receptor (PAR) 1. This study demonstrates that thrombin cleaves Jagged1 in its extracellular domain. The sJ1 form produced as a result of thrombin cleavage inhibits Notch-mediated CBF1/Suppressor of Hairless [(Su(H)]/Lag-1-dependent transcription and induces FGF1 expression and release. The overexpression of Jagged1 in PAR1 null cells results in a rapid thrombin-induced export of FGF1. These data demonstrate the existence of novel cross-talk between thrombin, FGF, and Notch signaling pathways, which play important roles in vascular formation and remodeling. INTRODUCTIONFibroblast growth factor (FGF) family members exhibit a variety of biological activities. During embryogenesis, they regulate mesoderm induction, neurulation, and formation of the circulatory and skeletal systems (Fallon et al., 1994;Friesel and Maciag, 1999). During postnatal development, they play a crucial role in angiogenesis, tissue regeneration, inflammation, and pathogenesis of some tumors (Christofori and Luef, 1997;Friesel and Maciag, 1999;Woolley et al., 2000;Javerzat et al., 2002;Okunieff et al., 2003). The biological effects of FGFs are mediated through the activation of four transmembrane phosphotyrosine kinase receptors (FGFR1-4) (McKeehan et al., 1998), with the participation of cell surface proteoglycans (Ornitz and Itoh, 2001), and consequently require FGF release. FGF1 is a potent proangiogenic factor, which supports the survival of endothelial cells in vitro, stimulates the growth of vessels, and enhances the repair of infarctic lesions in vivo (Sellke et al., 1996;Schumacher et al., 1998;Friesel and Maciag, 1999;Buehler et al., 2002). FGF1 lacks a signal peptide in its primary structure (Friesel and Maciag, 1999), and, similar to other signal peptide-less extracellular regulatory proteins, it undergoes nonclassical export (for review, see Prudovsky et al., 2003;Nickel, 2005;Prudovsky et al., 2008).Thrombin, the key protease of the blood coagulation cascade, induces the expression of several growth factors (Bassus et al., 2001;Cucina et al., 2002;Cao et al., 2006) and exhibits proangiogenic activity (Steinhoff et al., 2005). We recently demonstrated that thrombin, through activation of the protease-activated receptor (PAR) 1, rapidly induces FGF1 expression and its release under nonstress conditions, revealing an interplay between thrombin signaling and nonclassical FGF1 release (Duarte et al., 2006). PAR1 is activated through the proteolyti...

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R136K fibroblast growth factor-1 mutant induces heparin-independent migration of endothelial cells through fibrin glue

Cited by 27 publications

References 14 publications

Fibrin glue as a drug delivery system

Fibrin glue as a drug delivery system

Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering

Novel Cross-Talk between Three Cardiovascular Regulators: Thrombin Cleavage Fragment of Jagged1 Induces Fibroblast Growth Factor 1 Expression and Release

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