Mechanism Identified Behind Impaired Wound Healing in Diabetics

Curated by Claudia Shannon / Research Scientist / ishonest

About 15% of diabetics will have a non-healing wound at some point in their lifetime, and in some cases, these non-healing open ulcers can be so severe that they lead to amputations.

In 2013, a study found – contrary to previous research – that the Foxo1 molecule promotes healing by both protecting cells against oxidative stress and inducing a molecule called TGF-ß1 that is critical for wound healing.

ishonest No.111 - Purge Impurities

Recommended
No.111 - Purge Impurities

The Penn team wanted to investigate whether these mechanisms are also implicated in the reduced capacity for wound healing among people with diabetes.

To do this, the researchers first created small wounds on the tongues of mice with diabetes and a control group of non-diabetic mice. The wounds of the diabetic mice – as might be expected – healed more slowly than the control mice.

The team then repeated this experiment in mice bred to lack Foxo1 in a type of cell called keratinocytes, which “fill in” the holes left by injuries. The researchers were surprised to find that the absence of the Foxo1 protein and FOXO1 gene in the keratinocytes appeared to cause the diabetic mice to heal more quickly.

Next, the team experimented with cells in culture. The researchers found that cells grown in a “high-sugar media” were less able to move and proliferate, compared with cells grown in standard solution.

Your skin has the power to fight fine lines: Catalyse your skin to do more

Learn more

The same slowed proliferation of cells was observed by the researchers in diabetic mice; because the cells were slow to proliferate, they closed the wound over the keratinocyte filling less quickly than cells in the non-diabetic mice. And, like the diabetic mice, this impaired proliferation was reduced when the researchers silenced Foxo1 in the cells.

FOXO1 fails to stimulate wound-healing molecule in diabetics

Further experiments demonstrated that two signaling molecules regulated by Foxo1, CCL20 and IL-36 are implicated in the reduced cell movement – and by extension, reduced wound healing – found in diabetics.

Although the FOXO1 gene normally stimulates production of the wound-healing molecule TGF-ß1, say the researchers, in the diabetic mice it failed to do so, instead stimulating production of CCL20 and IL-36. These proteins interfere with the migration of keratinocytes, turning FOXO1 from promoting healing to hindering it.

Study leader Dana T. Graves, professor in Penn Dental Medicine’s Department of Periodontics and vice dean for scholarship and research, says:

“In terms of a wound-healing response, it looks like Foxo1 might be one of the central regulators that are affected by the diabetic condition. This may make it a good drug target, which could possibly be administered locally to minimize systemic effects in diabetic wounds.”

Read more on: impaired


What we do

We make skincare treatments and customize them for your skin-related problems, genetics, lifestyle, and environment.

How you benefit

You get total control over your skincare and the choice to change your skin. An impossible has just become possible.

How Custom Beauty Works

Desktop Mobile Graphic
Take the Quiz

Tell us about your skin, general health, lifestyle, environment, and all your skin goals. The quiz takes 4-8 minutes.

Outline of microscope
Create Your Treatment

Our algorithm creates a unique routine with a few customized products. The algorithm uses 50+ years of skincare research.

Outlines of Packaging
Divide and Rule

Every product is designed for one problem. Apply the product when the problem appears. Much like you treat flu or headache.

Product Values

A family sharing common values functions effortlessly and effectively. So do our products. All our products share these values.

Outline of bulb
Precise

Typical skincare routines confuse your skin with 20-50 ingredients. Our custom routines contain 1-8 ingredients, sending clear signals to your body to use the ingredients and recover faster.

Outline of Green Leaf
Concentrated

Our skin can use only active ingredients, also called actives. Most products contain up to 10% actives, whereas our products contain at least 90% actives. You get better value. Your skin avoids junk food.

Get Started

Never Used Before

Take the quiz below and discover a customized treatment for your unique skin-related problems, lifestyle, and environment.

Know Your Treatment

Every treatment has a unique 3-digit ID. You can find the ID on the product label. Search the ID on top right corner or click below.

Targeted Solutions

If a particular skin problem is bothering you, browse our products for your specific problem. You can customize your routine later.