Tissue repair with a therapeutic transcription factor

被引:59
作者
Bryant, M [1 ]
Drew, GM [1 ]
Houston, P [1 ]
Hissey, P [1 ]
Campbell, CJ [1 ]
Braddock, M [1 ]
机构
[1] Glaxo Wellcome Res & Dev Ltd, Med Res Ctr, Vasc Dis Unit,Endothelial Gene Express Grp, Wound Healing & Tissue Regenerat Program, Stevenage SG1 2NY, Herts, England
关键词
D O I
10.1089/104303400750001444
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The healing of tissue involves a wide range of molecular, cellular, and physiological events that are coordinated in a temporally specific manner. The cellular transcription factor early growth response factor 1 (Egr-1) is expressed minutes after acute injury and serves to stimulate the production of a class of growth factors whose role is to promote tissue repair. We have studied the effects of Egr-1 expression at the site of dermal wounding in rodents. We find that Egr-1 promotes angiogenesis in vitro and in vivo, increases collagen production, and accelerates wound closure. These results show that Egr-1 gene therapy accelerates the normal healing process and raises the potential use of this therapeutic transcription factor for any aspect of tissue repair.
引用
收藏
页码:2143 / 2158
页数:16
相关论文
共 59 条
[41]   ACIDIC FIBROBLAST GROWTH-FACTOR ACCELERATES DERMAL WOUND-HEALING IN DIABETIC MICE [J].
MELLIN, TN ;
CASHEN, DE ;
RONAN, JJ ;
MURPHY, BS ;
DISALVO, J ;
THOMAS, KA .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1995, 104 (05) :850-855
[42]   NAB2: A transcriptional brake for activated gene expression in the vessel wall? [J].
Miano, JM ;
Berk, BC .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1009-1012
[43]  
PERTOVAARA L, 1994, J BIOL CHEM, V269, P6271
[44]   Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study [J].
Rees, RS ;
Robson, MC ;
Smiell, JM ;
Perry, BH .
WOUND REPAIR AND REGENERATION, 1999, 7 (03) :141-147
[45]  
SAKAMOTO KM, 1991, ONCOGENE, V6, P867
[46]   New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury [J].
Santiago, FS ;
Lowe, HC ;
Kavurma, MM ;
Chesterman, CN ;
Baker, A ;
Atkins, DG ;
Khachigian, LM .
NATURE MEDICINE, 1999, 5 (11) :1264-1269
[47]   Fluid shear stress activation of egr-1 transcription in cultured human endothelial and epithelial cells is mediated via the extracellular signal-related kinase 1/2 mitogen-activated protein kinase pathway [J].
Schwachtgen, JL ;
Houston, P ;
Campbell, C ;
Sukhatme, V ;
Braddock, M .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (11) :2540-2549
[48]  
SCHWACHTGEN JL, 1999, DNA SEQUENCE, V10, P429
[49]   Vascular smooth muscle cells express the transcriptional corepressor NAB2 in response to injury [J].
Silverman, ES ;
Khachigian, LM ;
Santiago, FS ;
Williams, AJ ;
Lindner, V ;
Collins, T .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (04) :1311-1317
[50]   Inducible PDGF A-chain transcription in smooth muscle cells is mediated by Egr-1 displacement of Sp1 and Sp3 [J].
Silverman, ES ;
Khachigian, LM ;
Lindner, V ;
Williams, AJ ;
Collins, T .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1997, 273 (03) :H1415-H1426