Diabetes & metabolic syndrome · 2022
Notch signaling: A possible therapeutic target and its role in diabetic foot ulcers.
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Begum Farmiza, Keni Raghuvir, Ahuja Tejas N, Beegum Fathima, Nandakumar Krishnadas, Shenoy Rekha R
Аннотация
BACKGROUND & AIM: Diabetic foot ulcers are major cause of lower limb amputations in the diabetic population. The major factors that play a role in causing the delay of the process of healing in diabetic foot ulcers broadly are decreased angiogenesis, reduced proliferation and migration of keratinocytes/fibroblasts. The typical wound healing process has four phases which are overlapping with each other thus making the healing even more complex. Hence it is essential to identify a therapeutic target that involves the regulation of the cellular factors involved in healing and helps to increase angiogenesis and can regulate all four phases accordingly.
METHOD: Literature review involved a search of the databases namely, PubMed, Cochrane, EMBASE, and Web of Science database. Articles were identified and retrieved that specifically dealt with Notch as a target in healing of wounds and its mechanism of action on various cells and phases of healing.
RESULTS: Notch is a cell surface receptor which interacts with transmembrane ligands of the nearby cells and is involved in cell proliferation, differentiation, cell fate and death. It is also involved in cell-to-cell communication, cell signaling, and various phases of development. There exist four known notch genes and five ligands which interact with notch proteins. Hyperglycemia plays a role in the activation of the notch receptor thus causing the release of inflammatory mediators via macrophages. As notch can regulate macrophage-mediated inflammation it can serve as a therapeutic target for diabetic foot ulcers.
CONCLUSION: This review focuses on the effect of notch on various cell mediators and phases of diabetic wound healing and deals with how notch activation or inhibition can serve as a potential therapeutic target for healing diabetic foot ulcers.
METHOD: Literature review involved a search of the databases namely, PubMed, Cochrane, EMBASE, and Web of Science database. Articles were identified and retrieved that specifically dealt with Notch as a target in healing of wounds and its mechanism of action on various cells and phases of healing.
RESULTS: Notch is a cell surface receptor which interacts with transmembrane ligands of the nearby cells and is involved in cell proliferation, differentiation, cell fate and death. It is also involved in cell-to-cell communication, cell signaling, and various phases of development. There exist four known notch genes and five ligands which interact with notch proteins. Hyperglycemia plays a role in the activation of the notch receptor thus causing the release of inflammatory mediators via macrophages. As notch can regulate macrophage-mediated inflammation it can serve as a therapeutic target for diabetic foot ulcers.
CONCLUSION: This review focuses on the effect of notch on various cell mediators and phases of diabetic wound healing and deals with how notch activation or inhibition can serve as a potential therapeutic target for healing diabetic foot ulcers.