Constitutive expression of hypoxia-inducible factor-1 α in keratinocytes during the repair of skin wounds in horses.

This research article investigates the role of the hypoxia-inducible factor-1 α (HIF1α), a protein that response to low oxygen levels, in the process of wound healing in horses specifically focusing on body and limb wounds. Notably, it examines how this factor varies across different stages of wound repair, its localization within the skin, and its effectiveness in regulating important target genes.

Research Method and Findings

• The researchers wanted to understand the role of HIF1α during the wound healing process on horses, given the fact that a brief state of low oxygen, or hypoxia, tends to exist within skin wounds, and is believed to facilitate the healing process. For this reason, the research concentrates on the molecular response to hypoxia in healing horse body and limb wounds.
• HIF1α protein expression was examined at various stages of healing through Western blotting and immunofluorescence. Interestingly, strong HIF1α expression was found in intact skin but it decreased dramatically once the skin was wounded. This was contrary to the expectation of increased expression in response to the hypoxic state of the wounded tissue.
• As healing progressed, HIF1α levels increased in correlation with the process of epithelialization, which is the growth of new skin over a wound. This increase was observed to be quicker in body wounds than in limb wounds.
• The location of HIF1α was found to be predominantly within the keratinocyte layer of the skin, which is the outermost layer that produces keratin. There, it was continuously present throughout the healing process implying that it was expressed independently of the hypoxic state.

Impacts on Other Genes

• Beyond the study of HIF1α, the research also explored the gene, cyclin-dependent kinase inhibitor 1A (CDKN1A). This gene demonstrated an expression pattern similar to HIF1α throughout the healing process, suggesting that HIF1α might be regulating its continuous expression.
• In contrast, the expression patterns of the HIF1α target genes known as vascular endothelial growth factor A (VEGFA) and solute carrier family 2 (facilitated glucose transporter) member 1 (SLC2A1), weren’t similar to HIF1α at the mRNA level.
• Governed by these findings, the researchers concluded that in horses, HIF1α is expressed in a continuous and hypoxia-independent manner in equine keratinocytes in both intact and wounded skin and that this may play a role in regulating the expression of CDKN1A in the same cell type.