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Publication : HOXA3 accelerates wound healing in diabetic and aged non-diabetic mammals.

First Author  Parella K Year  2023
Journal  Sci Rep Volume  13
Issue  1 Pages  9923
PubMed ID  37337031 Mgi Jnum  J:338632
Mgi Id  MGI:7492961 Doi  10.1038/s41598-023-36933-4
Citation  Parella K, et al. (2023) HOXA3 accelerates wound healing in diabetic and aged non-diabetic mammals. Sci Rep 13(1):9923
abstractText  Chronic wounds are characterized by a persistent, hyper-inflammatory environment that prevents progression to regenerative wound closure. Such chronic wounds are especially common in diabetic patients, often requiring distal limb amputation, but occur in non-diabetic, elderly patients as well. Induced expression of HoxA3, a member of the Homeobox family of body patterning and master regulatory transcription factors, has been shown to accelerate wound closure in diabetic mice when applied topically as a plasmid encased in a hydrogel. We now provide independent replication of those foundational in vivo diabetic wound closure studies, observing 16% faster healing (3.3 mm wounds vs 3.9 mm wounds at Day 9 post original injury of 6 mm diameter) under treatment with observable microscopic benefits. We then expand upon these findings with minimal dose threshold estimation of 1 mug HoxA3 plasmid delivered topically at a weekly interval. Furthermore, we observed similarities in natural wound healing rates between aged non-diabetic mice and young diabetic mice, which provided motivation to test topical HoxA3 plasmid in aged non-diabetic mice. We observed that HoxA3 treatment achieved complete wound closure (0 mm diameter) at 2 weeks whereas untreated wounds were only 50% closed (3 mm wound diameter). We did not observe any gross adverse effects macroscopically or via histology in these short studies. Whether as a plasmid or future alternative modality, topical HoxA3 is an attractive translational candidate for chronic wounds.
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