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Research Article Free access | 10.1172/JCI119118

Particle-mediated gene transfer with transforming growth factor-beta1 cDNAs enhances wound repair in rat skin.

S I Benn, J S Whitsitt, K N Broadley, L B Nanney, D Perkins, L He, M Patel, J R Morgan, W F Swain, and J M Davidson

Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2561, USA.

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Published December 15, 1996 - More info

Published in Volume 98, Issue 12 on December 15, 1996
J Clin Invest. 1996;98(12):2894–2902. https://doi.org/10.1172/JCI119118.
© 1996 The American Society for Clinical Investigation
Published December 15, 1996 - Version history
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Abstract

Based on preliminary but variable results with direct DNA transfer into wounds, we evaluated in vivo gene transfer by particle-mediated DNA delivery to rat skin to determine whether overexpression of TGF-beta1 at the site of skin incisions would result in a significant improvement in repair. Optimization of the method with viral promoter-luciferase reporter constructs indicated that expression of luciferase activity persisted up to 5 d and was promoter, pressure, and site dependent (ventral > dorsal). Using cytomegalovirus (CMV)-driven human alpha1-antitrypsin, transgene expression was immunolocalized within keratinocytes of the stratum granulosum at 24 h. We measured tensile strength of skin incisions at 11-21 d in both normal and diabetic rats transfected with TGF-beta1 expression vectors at surgery. Native murine TGF-beta1 under an SV40 promoter produced positive effects, while wound strengthening was more pronounced in diabetic animals using a CMV-driven construct. Transfection of rat skin with constitutively active, mutant porcine TGF-beta1 under the control of the CMV and Moloney murine leukemia virus promoters significantly increased tensile strength up to 80% for 14-21 d after surgery. Transfection 24 h before surgery was more effective. Particle-mediated gene delivery can be used to deliver viral promoter-cytokine expression constructs into rat skin in a safe, efficient, and reproducible fashion. The extent of wound repair, as evidenced by enhanced tensile strength, can be markedly improved in tissues transfected with TGF-beta1 expression constructs.

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