A group of stomatologists at the University of Pennsylvania in the United States have identified a key molecule, Foxo1, that is closely related to the difficulty of wound healing in the case of diabetes. This study was published in the most recent issue of Diabetes.
One of the many complications of diabetes is the slow healing of the wound. About 15% of people with diabetes have to endure the pain and trouble that the wound can't heal, and in some cases, these open ulcers on the skin can lead to the final amputation. Researchers have been looking for reasons for many years and found that many factors are involved in the process. But the main factors and specific mechanisms are not clear, let alone the targeted treatment of these stubborn wounds.
In fact, in 2013, the researchers discovered a molecule called Foxo1 that is involved in the healing process - it protects cells from oxidative stress and induces TGF-β1, another molecule that plays a key role in the healing process. . The researchers then tested whether Foxo1 had the same effect on poor healing in diabetics.
Diabetic mice and normal mice were used in the experiment to scratch the tongue of the mice under anesthesia. Surprisingly, wound healing in keratinocytes lacking Foxo1 expression was significantly improved, whereas in normal mice in the same condition, healing was slowed.
What kind of mechanism is responsible for the opposite function of Foxo1 in different mice? Researchers have found that Foxo1 can stimulate the expression of two signaling molecules CCL20 and IL-36γ in the case of diabetes. These two cells can interfere with cell migration. A very important process of wound healing is to fill the gaps in the epidermis caused by the movement and proliferation of keratinocytes, which has a great degree of protection for the wound. It was observed in the experiment that keratinocyte movement and proliferation were inhibited in diabetic mice. When the expression of Foxo1 was inhibited, the inhibition of cell activity was relieved, which directly increased the healing rate. In normal mice, the main role of Foxo1 is to stimulate the protein TGF-β1 to help wound healing. After the inhibition of Foxo1, the wound healed as expected was slowed down. However, in the case of diabetes, an increase in TGF-β1 induced by Foxo1 was not detected.
This finding determines how Foxo1 is involved in mucosal wound healing. Its role can change due to diabetes or normal populations - under normal conditions, it can promote wound healing; in the case of diabetes, it is inhibitory. Therefore, in the case of diabetes, Foxo1 can be used as a new drug target, and topical drug inhibition of Foxo1 expression may contribute to the healing of wounds in diabetic patients.
Source: CFDA
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