Protein that promotes healing inhibits it in diabetic patients, study shows

A protein that helps wounds heal actively inhibits this process when blood sugar levels are high, according to research that could explain a 'previously unrecognised' mechanism for delayed healing in patients with diabetes.

Diabetic foot ulcer: protein affects healing process (Photo: Science Photo Library)
Diabetic foot ulcer: protein affects healing process (Photo: Science Photo Library)

In animal-model studies, University of Pennsylvania researchers found that the forkhead box O1 (FOXO1) protein – which normally helps trigger the healing process – promotes expression of two genes that inhibit the migration of skin cells to wound sites when exposed to high-glucose conditions.

This could explain why simple wounds in diabetes patients do not close up as quickly as in non-diabetics, and suggests that treatments to inhibit FOXO1 could be a beneficial therapeutic option for diabetes patients in the future.

Because wounds take longer to heal in diabetics, it is easier for bacteria to take hold and cause chronic infection, which can lead to diabetic ulcers and – in extreme cases – require amputation.

Differential wound healing

FOXO1 normally orchestrates an important step in the early healing process by activating the TGFB1 gene, which in turn promotes pro-healing responses and causes keratinocytes (skin cells) to migrate to wound sites.

‘Whether FOXO1 is beneficial or harmful, whether it promotes healing or inhibits healing, depends on the environment of the cell,’ said lead researcher Dr Dana Graves.

The results, published the Journal of Cell Biology, corroborate previous studies which have shown that insulin stimulates wound healing in diabetics.

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