Discordant effects of a soluble VEGF receptor on wound healing and angiogenesis.

Abstract:

:Soluble receptors to vascular endothelial growth factor (VEGF) can inhibit its angiogenic effect. Since angiogenesis is involved in wound repair, we hypothesized that adenovirus-mediated gene transfer of a soluble form of VEGF receptor 2 (Flk-1) would attenuate wound healing in mice. C57Bl/6J and genetically diabetic (db/db) mice (each n=20) received intravenous (i.v.) injections of recombinant adenoviruses (10(9) PFU) encoding the ligand-binding ectodomain of VEGF receptor 2 (Flk-1) or cDNA encoding the murine IgG2alpha Fc fragment (each n=10). At 4 days after gene transfer, two full-thickness skin wounds (0.8 cm) were created on the dorsum of each animal. Wound closure was measured over 9-14 days after which wounds were resected for histological analysis. Prior to killing, fluorescent microspheres were systemically injected for quantitation of wound vascularity. Single i.v. injections of adenoviruses encoding soluble Flk-1 significantly decreased wound angiogenesis in both wild-type and diabetic mice. Fluorescence microscopy revealed a 2.0-fold (wild type) and 2.9-fold (diabetic) reduction in wound vascularity in Flk-1-treated animals (p<0.05). Impairment of angiogenesis was confirmed by CD31 immunohistochemistry. Interestingly, despite significant reductions in wound vascularity, wound closure was not grossly delayed. Our data indicates that while VEGF function is essential for optimal wound angiogenesis, it is not required for wound closure.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Jacobi J,Tam BY,Sundram U,von Degenfeld G,Blau HM,Kuo CJ,Cooke JP

doi

10.1038/sj.gt.3302162

keywords:

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

302-9

issue

3

eissn

0969-7128

issn

1476-5462

pii

3302162

journal_volume

11

pub_type

杂志文章
  • In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes.

    abstract::Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 (Ex4) have displayed potent glucose homeostasis-modulating characteristics in type 2 diabetes (T2D). However, there are few reports of effectiveness in type 1 diabetes (T1D) therapy, where there is massive loss of beta cells. We previously described a novel GL...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302944

    authors: Soltani N,Kumar M,Glinka Y,Prud'homme GJ,Wang Q

    更新日期:2007-06-01 00:00:00

  • Formation of LID vector complexes in water alters physicochemical properties and enhances pulmonary gene expression in vivo.

    abstract::There is currently an urgent need to develop efficient gene-delivery systems for the lung that are free of inflammatory effects. The LID vector is a synthetic gene delivery system, comprised of lipofectin (L), an integrin-targeting peptide (I) and DNA (D) that has previously been shown to have high transfection effici...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301963

    authors: Jenkins RG,Meng QH,Hodges RJ,Lee LK,Bottoms SE,Laurent GJ,Willis D,Ayazi Shamlou P,McAnulty RJ,Hart SL

    更新日期:2003-06-01 00:00:00

  • Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats.

    abstract::Intracerebral administration of recombinant adeno-associated vector (AAV) has been performed in several clinical trials. However, delivery into the brain requires multiple injections and is not efficient to target the spinal cord, thus limiting its applications. To assess widespread and less invasive strategies, we te...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.121

    authors: Hordeaux J,Dubreil L,Deniaud J,Iacobelli F,Moreau S,Ledevin M,Le Guiner C,Blouin V,Le Duff J,Mendes-Madeira A,Rolling F,Cherel Y,Moullier P,Colle MA

    更新日期:2015-04-01 00:00:00

  • Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo.

    abstract::We have assessed whether magnetic forces (magnetofection) can enhance non-viral gene transfer to the airways. TransMAG(PEI), a superparamagnetic particle was coupled to Lipofectamine 2000 or cationic lipid 67 (GL67)/plasmid DNA (pDNA) liposome complexes. In vitro transfection with these formulations resulted in approx...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302803

    authors: Xenariou S,Griesenbach U,Ferrari S,Dean P,Scheule RK,Cheng SH,Geddes DM,Plank C,Alton EW

    更新日期:2006-11-01 00:00:00

  • Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus.

    abstract::The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this re...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Barr E,Carroll J,Kalynych AM,Tripathy SK,Kozarsky K,Wilson JM,Leiden JM

    更新日期:1994-01-01 00:00:00

  • Muscle-derived stem cells.

    abstract::The existence of cells with stem cell-like abilities derived from various tissues can now be extended to include the skeletal muscle compartment. Although researchers have focused on the utilization of these cells with regard to their myogenic capacity, initially exploring more efficient cellular therapy treatments fo...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3301719

    authors: Jankowski RJ,Deasy BM,Huard J

    更新日期:2002-05-01 00:00:00

  • Clinical retroviral vector production: step filtration using clinically approved filters improves titers.

    abstract::Production of retroviral vectors for clinical use requires removal of cells and cellular debris. We combined a series of filters of decreasing pore size using commercially available blood banking filters approved for clinical use. The collection bag and filters can be connected to create a sterile, closed system using...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301328

    authors: Reeves L,Cornetta K

    更新日期:2000-12-01 00:00:00

  • Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro.

    abstract::Prostate cancer is the most common cancer in men of the western world. To date, no effective treatment exists for metastatic prostate cancer and consequently, there is an urgent need to develop new and improved therapeutics. In recent years, the therapeutic potential of RNA interference (RNAi) has been extensively exp...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.50

    authors: Evans JC,McCarthy J,Torres-Fuentes C,Cryan JF,Ogier J,Darcy R,Watson RW,O'Driscoll CM

    更新日期:2015-10-01 00:00:00

  • Electropermeabilization of skeletal muscle enhances gene transfer in vivo.

    abstract::This work demonstrates that electrical muscle stimulation markedly increases the transfection efficiency of an intramuscular injection of plasmid DNA. In soleus or extensor digitorum longus muscles of adult rats the percentage of transfected fibers increased from about 1 to more than 10. The number of transfected fibe...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300847

    authors: Mathiesen I

    更新日期:1999-04-01 00:00:00

  • T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer.

    abstract::We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301687

    authors: Martinet O,Divino CM,Zang Y,Gan Y,Mandeli J,Thung S,Pan PY,Chen SH

    更新日期:2002-06-01 00:00:00

  • Restoration of all dystrophin protein interactions by functional domains in trans does not rescue dystrophy.

    abstract::Rescue of dystrophic skeletal muscle in mdx and utrophin/dystrophin-deficient (dko) mouse models by reintroduction of dystrophin has validated gene therapy as a potential therapeutic approach for Duchenne muscular dystrophy. However, the size of the dystrophin gene exceeds the capacity of adeno-associated viral (AAV) ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302686

    authors: Gardner KL,Kearney JA,Edwards JD,Rafael-Fortney JA

    更新日期:2006-05-01 00:00:00

  • In vivo suppression of restenosis in balloon-injured rat carotid artery by adenovirus-mediated gene transfer of the cell surface-directed plasmin inhibitor ATF.BPTI.

    abstract::Injury-induced neointimal development results from migration and proliferation of vascular smooth muscle cells (SMC). Cell migration requires controlled proteolytic degradation of extracellular matrix surrounding the cell. Plasmin is a major contributor to this process by degrading various matrix proteins directly, or...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301437

    authors: Lamfers ML,Lardenoye JH,de Vries MR,Aalders MC,Engelse MA,Grimbergen JM,van Hinsbergh VW,Quax PH

    更新日期:2001-04-01 00:00:00

  • Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector.

    abstract::One factor limiting the ability to modify human repopulating hematopoietic cells genetically with retroviral vectors is the relatively low expression of the cognate viral receptor. We have tested sequential transduction of human hematopoietic cells with an adenoviral vector encoding the ecotropic retroviral receptor f...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300974

    authors: Nathwani AC,Persons DA,Stevenson SC,Frare P,McClelland A,Nienhuis AW,Vanin EF

    更新日期:1999-08-01 00:00:00

  • Evaluation of prenatal intra-amniotic LAMB3 gene delivery in a mouse model of Herlitz disease.

    abstract::Prenatal gene therapy has been considered for Herlitz junctional epidermolysis bullosa (H-JEB), a lethal genodermatosis caused by the absence of any of the three subunits of laminin-5, resulting from birth in widespread blistering and erosions of skin and mucosae. To investigate this strategy in an animal model, adeno...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302832

    authors: Mühle C,Neuner A,Park J,Pacho F,Jiang Q,Waddington SN,Schneider H

    更新日期:2006-12-01 00:00:00

  • Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins.

    abstract::Catheter-based percutaneous transluminal gene delivery (PTGD) into the coronary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhesion of replication...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301079

    authors: Boekstegers P,von Degenfeld G,Giehrl W,Heinrich D,Hullin R,Kupatt C,Steinbeck G,Baretton G,Middeler G,Katus H,Franz WM

    更新日期:2000-02-01 00:00:00

  • Systemic administration of naked plasmid encoding hepatocyte growth factor ameliorates chronic renal fibrosis in mice.

    abstract::The progression of chronic renal diseases is considered as an irreversible process that eventually leads to end-stage renal failure characterized by extensive tissue fibrosis. At present, chronic renal fibrosis is incurable and the incidence of affected patients is on the rise worldwide. In this study, we demonstrate ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301545

    authors: Yang J,Dai C,Liu Y

    更新日期:2001-10-01 00:00:00

  • High and prolonged sulfamidase secretion by the liver of MPS-IIIA mice following hydrodynamic tail vein delivery of antibiotic-free pFAR4 plasmid vector.

    abstract::Mucopolysaccharidosis type IIIA (MPS-IIIA) or Sanfilippo A syndrome is a lysosomal storage genetic disease that results from the deficiency of the N-sulfoglucosamine sulfohydrolase (SGSH) protein, a sulfamidase required for the degradation of heparan sulfate glycosaminoglycans (GAGs). The accumulation of these macromo...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.75

    authors: Quiviger M,Arfi A,Mansard D,Delacotte L,Pastor M,Scherman D,Marie C

    更新日期:2014-12-01 00:00:00

  • Long-term gene expression from autonomously replicating vectors in mammalian cells.

    abstract::We tested the longevity of gene expression provided by autonomously replicating vectors. The vectors contain segments of human genomic DNA that provide efficient replication initiation and sequences derived from Epstein-Barr virus that provide nuclear retention. In order to monitor gene expression, the vectors also ca...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Wohlgemuth JG,Kang SH,Bulboaca GH,Nawotka KA,Calos MP

    更新日期:1996-06-01 00:00:00

  • Gene therapy for pancreatitis pain.

    abstract::Pancreatic cancer and chronic pancreatitis are clinical syndromes associated with severe pain that is difficult to manage. Thus, seeking additional pain reduction therapies is warranted. Excessive alcohol consumption over an extended period of time is the primary causal agent in pancreatitis. The efficacy of a replica...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/gt.2009.27

    authors: Westlund KN

    更新日期:2009-04-01 00:00:00

  • Articular cartilage repair by genetically modified bone marrow aspirate in sheep.

    abstract::Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was p...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.16

    authors: Ivkovic A,Pascher A,Hudetz D,Maticic D,Jelic M,Dickinson S,Loparic M,Haspl M,Windhager R,Pecina M

    更新日期:2010-06-01 00:00:00

  • hTERT promoter induces tumor-specific Bax gene expression and cell killing in syngenic mouse tumor model and prevents systemic toxicity.

    abstract::We recently showed that the human telomerase reverse transcriptase (hTERT) promoter induces tumor-specific Bax gene expression and selectively kills various human cancer cells both in vitro and in xenograft tumors. However, it remains unclear whether the hTERT promoter can be used to induce transgene expression in syn...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301619

    authors: Gu J,Andreeff M,Roth JA,Fang B

    更新日期:2002-01-01 00:00:00

  • Beta defensin-3 engineered epidermis shows highly protective effect for bacterial infection.

    abstract::Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302472

    authors: Sawamura D,Goto M,Shibaki A,Akiyama M,McMillan JR,Abiko Y,Shimizu H

    更新日期:2005-05-01 00:00:00

  • RNAi-mediated gene silencing in tumour tissue using replication-competent retroviral vectors.

    abstract::RNAi represents a powerful technology to specifically downregulate the expression of target genes. For cancer research and therapy, an efficient in vivo delivery system is supposed to distribute RNAi to all tumour cells upon systemic administration. We present replication-competent murine leukaemia virus (MLV) vectors...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2011.48

    authors: Schaser T,Wrede C,Duerner L,Sliva K,Cichutek K,Schnierle B,Buchholz CJ

    更新日期:2011-10-01 00:00:00

  • Identification of an alveolar type I epithelial cell-specific DNA nuclear import sequence for gene delivery.

    abstract::The ability to restrict gene delivery and expression to particular cell types is of paramount importance for many types of gene therapy, especially in the lung. The alveolar epithelial type I (ATI) cell, in particular, is an attractive cell type to target, as it comprises 95% of the internal surface area of the lung. ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2016.52

    authors: Gottfried L,Lin X,Barravecchia M,Dean DA

    更新日期:2016-10-01 00:00:00

  • Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium.

    abstract::Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for t...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301348

    authors: Connor RJ,Engler H,Machemer T,Philopena JM,Horn MT,Sutjipto S,Maneval DC,Youngster S,Chan TM,Bausch J,McAuliffe JP,Hindsgaul O,Nagabhushan TL

    更新日期:2001-01-01 00:00:00

  • Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review.

    abstract::Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leadin...

    journal_title:Gene therapy

    pub_type: 信件,评审

    doi:10.1038/s41434-018-0004-0

    authors: Sampara P,Banala RR,Vemuri SK,Av GR,Gpv S

    更新日期:2018-04-01 00:00:00

  • Transfer of the murine interleukin-12 gene in vivo by a Semliki Forest virus vector induces B16 tumor regression through inhibition of tumor blood vessel formation monitored by Doppler ultrasonography.

    abstract::To elucidate further the potential of a Semliki Forest virus (SFV) vector in vivo for gene therapy, we constructed a vector, SFV-IL12, to transfer murine IL-12 genes into tumors. A single intratumoral injection of established B16 murine melanoma with SFV-IL12 resulted in a significant inhibition of tumor growth, while...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300841

    authors: Asselin-Paturel C,Lassau N,Guinebretière JM,Zhang J,Gay F,Bex F,Hallez S,Leclere J,Peronneau P,Mami-Chouaib F,Chouaib S

    更新日期:1999-04-01 00:00:00

  • Antigen design enhances the immunogenicity of Semliki Forest virus-based therapeutic human papillomavirus vaccines.

    abstract::Cellular immunity against cancer can be achieved with viral vector- and DNA-based immunizations. In preclinical studies, cancer vaccines are very potent, but in clinical trials these potencies are not achieved yet. Thus, a rational approach to improve cancer vaccines is warranted. We previously demonstrated that the r...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.24

    authors: Ip PP,Boerma A,Walczak M,Oosterhuis K,Haanen JB,Schumacher TN,Nijman HW,Daemen T

    更新日期:2015-07-01 00:00:00

  • Pseudotyping of Moloney leukemia virus-based retroviral vectors with simian immunodeficiency virus envelope leads to targeted infection of human CD4+ lymphoid cells.

    abstract::In view of our recent findings that a truncated form of the envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) was efficiently incorporated into MoMLV particles, we studied the generation of Moloney murine leukemia virus (MoMLV)/simian immunodeficiency virus (SIV) pseudotypes. Unlike HIV-1, bot...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300603

    authors: Indraccolo S,Minuzzo S,Feroli F,Mammano F,Calderazzo F,Chieco-Bianchi L,Amadori A

    更新日期:1998-02-01 00:00:00

  • Tf-lipoplex-mediated NGF gene transfer to the CNS: neuronal protection and recovery in an excitotoxic model of brain injury.

    abstract::The development of efficient systems for in vivo gene transfer to the central nervous system (CNS) may provide a useful therapeutic strategy for the alleviation of several neurological disorders. In this study, we evaluated the feasibility of nonviral gene therapy to the CNS mediated by cationic liposomes. We present ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302516

    authors: da Cruz MT,Cardoso AL,de Almeida LP,Simões S,de Lima MC

    更新日期:2005-08-01 00:00:00