HoxD3 accelerates wound healing in diabetic mice

Journal Article · Mon Dec 01 04:00:00 EST 2003 · American Journal of Pathology

DOI:https://doi.org/10.1016/S0002-9440(10)63597-3· OSTI ID:825329

Hansen, Scott L ^[1]; Myers, Connie A; Charboneau, Aubri; Young, David M; and Boudreau, Nancy

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1. LBNL Library

Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: US Department of Energy (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 825329
• Report Number(s): LBNL--55496
• Journal Information: American Journal of Pathology, Journal Name: American Journal of Pathology Journal Issue: 6 Vol. 163; ISSN AJPAA4; ISSN 0002-9440
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACCELERATION
CLOSURES
COLLAGEN
DEPOSITION
DNA
FIBROBLASTS
GENES
HEALING
MICE
PLASMIDS
REPAIR
STIMULATION
SYNTHESIS
TARGETS
TRANSCRIPTION FACTORS
WOUNDS