Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice.

Tsuboi, Ryoji; Rifkin, Daniel B.

doi:10.1084/jem.172.1.245

Cited by 284 publications

(192 citation statements)

References 24 publications

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“…In animal models, FGF has been shown to enhance angiogenesis, granulation, tissue formation, epithelial growth and wound healing in diabetes and ischemia. 33,34 In a human clinical trial using recombinant FGF for the treatment of chronic pressure sores resulted in modest reductions in wound volume and increased the number of ®broblasts and capillaries in the wound.…”

Section: Discussionmentioning

confidence: 99%

Traumatic arteriogenic erectile dysfunction: a rat model

et al. 2001

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We developed a rat model of traumatic arteriogenic erectile dysfunction (ED) for the study of vasculogenic ED. Bilateral ligation of the internal iliac artery was performed on 30 three-month old male Sprague ± Dawley rats as an experimental group. The control group consisted of 12 rats which underwent dissection of the internal iliac artery without ligation. Before their euthanization at 3 days, 7 days, and 1 month (10 rats in the experimental group and four rats in the control group at each time point), erectile function was assessed by electrostimulation of the cavernous nerves. Penile tissues were collected for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining, trichrome staining, electron microscopy and RT-PCR for transforming growth factor beta (TGF-b1), insulin like growth factor-I (IGF-I) and ®broblast growth factors (FGF) mRNA expression. Electrostimulation of the cavernous nerves revealed a highly signi®cant declining of the intracavernous pressure after 3 and 7 days. No signi®cant recovery of erectile function was noted at 1 month. Histology showed degeneration of the dorsal nerve ®bers in all experimental rats. There was little decrease in the bulk of intracavernous smooth muscle in the experimental rats euthanazed 7 and 30 days. NADPH diaphorase staining revealed a signi®cant decrease in nitric oxide synthase (NOS) containing nerve ®bers in the dorsal and intracavernosal nerves in all rats in the experimental group. Electron microscopy showed a variety of changes such as collapse of sinusoids, increased cell debris, ®broblast and myo®broblast loss, intracellular deposition of fat and collagen and fatty degeneration. RT-PCR revealed up-regulation of TGF-b1 after 3 days but not after 7 days or 1 month. There is no signi®cant difference in IGF-I or FGF expression between the experimental and control group. Bilateral ligation of internal iliac arteries produces a reliable animal model for traumatic arteriogenic ED. Further studies are needed to investigate the molecular mechanism of ED in this model.

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Section: Discussionmentioning

confidence: 99%

Traumatic arteriogenic erectile dysfunction: a rat model

et al. 2001

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“…40,52,53 Complementary to this, FGF2-null mice show delayed wound healing. 27 Based on these observations, we investigated the impact of BP1 transgene expression on the healing of full-thickness skin wounds.…”

Section: Macroscopic Analysismentioning

confidence: 99%

“…Serial paraffin-embedded tissue sections (5 m) were stained with hematoxylin and eosin (H&E) and analyzed by serial sectioning as described in Ref. 40 The percentage of re-epithelialization was calculated with the following formula: 100 ϫ {[(wound diameter) Ϫ (epidermal gap)]/(wound diameter)}, where the epidermal gap is the distance between opposite epithelial tongues. The number of capillaries, infiltrating cells (macrophages and fibroblasts), and the re-epithelialization were measured by two observers blinded to the design.…”

Section: Wound Healing Assaymentioning

confidence: 99%

Impact of Fibroblast Growth Factor-Binding Protein–1 Expression on Angiogenesis and Wound Healing

Tassi

McDonnell

Gibby

et al. 2011

The American Journal of Pathology

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Fibroblast growth factors (FGFs) participate in embryonic development, in maintenance of tissue homeostasis in the adult, and in various diseases. FGF-binding proteins (FGFBP) are secreted proteins that chaperone FGFs stored in the extracellular matrix to their receptor, and can thus modulate FGF signaling. FGFBP1 (alias BP1, FGF-BP1, or HBp17) expression is required for embryonic survival, can modulate FGF-dependent vascular permeability in embryos, and is an angiogenic switch in human cancers. To determine the function of BP1 in vivo, we generated tetracycline-regulated conditional BP1 transgenic mice. BP1-expressing adult mice are viable, fertile, and phenotypically indistinguishable from their littermates. Induction of BP1 expression increased mouse primary fibroblast motility in vitro, increased angiogenic sprouting into subcutaneous matrigel plugs in animals and accelerated the healing of excisional skin wounds. FGF-receptor kinase inhibitors blocked these effects. Healing skin wounds showed increased macrophage invasion as well as cell proliferation after BP1 expression. Also, BP1 expression increased angiogenesis during the healing of skin wounds as well as after ischemic injury to hindlimb skeletal muscles. We conclude that BP1 can enhance FGF effects that are required for the healing and repair of injured tissues in adult animals. The family of fibroblast growth factors (FGFs) encompasses 18 distinct FGF receptor ligands, with a wide expression range and a significant role in angiogenesis, tumor progression, wound healing, and embryonic development.1-4 Many members of the FGF family, such as FGF1 and FGF2, are immobilized in the extracellular matrix (ECM) bound to heparan sulfate proteoglycans (HSPGs) and released from this storage site by proteases and heparanases. 4 -6 The involvement of carrier proteins that shuttle FGFs from their storage site to their receptors represents an alternative mode of regulation of FGF release from the ECM. 1,7 FGF-binding protein 1 (BP1, FGFBP1, FGF-BP1, or HBp17), 8 the best characterized of the three known secreted FGFBPs, 9 is an extracellular chaperone that binds FGF1, 2, 7, 10, and 22 in a reversible, noncovalent manner. 8,10 -12 Binding of the C-terminus of the BP1 protein is sufficient for its interaction with FGF2.13 After binding to BP1, the biochemical and biological activities of FGF are positively modulated.14 Several findings from different laboratories indicate that BP1 can contribute to embryonic development, 15 angiogenesis, tumor growth, and malignant progression, 11,12,14 -20 as well as the maintenance and reinnervation of the neuromuscular junction. 21 We reported earlier that expression of BP1 in SW13 cells induces FGF2 release from the cells, FGF-dependent colony formation in soft agar, and the growth of highly vascularized tumors in nude mice.11 In contrast, depletion of endogenous BP1 from ME180 cells was observed to reduce the release of ECM bound FGF2 into the cell supernatants and to increase FGF2 immobilized on the cell surface.16 Consisten...

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“…[3][4][5][6][7] Conversely, inhibitors of angiogenesis, such as TNP-470, delay wound repair in diabetic mice. 8 In humans, recombinant PDGF improved wound healing in patients suffering from cutaneous diabetic ulcers or pressure sores.…”

mentioning

confidence: 99%

Nicotine Accelerates Angiogenesis and Wound Healing in Genetically Diabetic Mice

Jacobi

Jang

Sundram

et al. 2002

The American Journal of Pathology

157

117

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Recently, we have discovered an endogenous cholinergic pathway for angiogenesis mediated by endothelial nicotinic acetylcholine receptors (nAChRs). Since angiogenesis plays a major role in wound repair, we hypothesized that activation of nAChRs with nicotine would accelerate wound healing in a murine excisional wound model. In genetically diabetic and control mice full-thickness skin wounds (0.8 cm) were created on the dorsum and topically treated over 7 days with either vehicle (phosphate-buffered saline, PBS) or nicotine (10 ؊8 mol/L, 10 ؊9 mol/L; each, n ‫؍‬ 5). Wound size was measured over 14 days followed by resection, histological analysis, and quantitation of vascularity. In diabetic animals an agonist (epibatidine, 10 ؊10 mol/L) or antagonist (hexamethonium, 10 ؊4 mol/L) of nAChRs as well as the positive control basic fibroblast growth factor (bFGF, 25 g/kg) were also tested. To further study the role of endothelial nAChRs in angiogenesis, we used an ex vivo vascular explant model. In diabetic mice wound healing was markedly impaired. Nicotine significantly accelerated wound healing as assessed by closure rate and histological score. The effects of nicotine were equal to bFGF and were mimicked by epibatidine and blocked by hexamethonium. Histomorphometry revealed increased neovascularization in animals treated with nicotine. Furthermore, capillary-like sprouting from vascular explants was significantly enhanced by nicotine. In conclusion, agonist-induced stimulation of nAChRs accelerates wound healing in diabetic mice by promoting angiogenesis. We have discovered a cholinergic pathway for angiogenesis that is involved in wound healing, and which is a potential target for therapeutic angiogenesis.

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Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice.

Cited by 284 publications

References 24 publications

Traumatic arteriogenic erectile dysfunction: a rat model

Traumatic arteriogenic erectile dysfunction: a rat model

Impact of Fibroblast Growth Factor-Binding Protein–1 Expression on Angiogenesis and Wound Healing

Nicotine Accelerates Angiogenesis and Wound Healing in Genetically Diabetic Mice

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