The Role of Intracellular Signaling Pathways in the Development of Trophic Pathologies of the Lower Extremities and Their Regeneration Under Type 2 Diabetes (Part 1)

Abstract

Introduction. This review article addresses the critical issue of the development and regeneration of chronic trophic ulcers in the context of type 2 diabetes. This pathological process is associated with inhibited cell proliferation, impaired differentiation of various cell types, and disrupted mechanisms that regulate cell death. An analysis of recent scientific literature also highlights the involvement of key intracellular signaling pathways in the development of chronic ulcerative pathologies of the lower extremities, as observed in both experimental animal models and patients with type II diabetes. Despite advancements, this issue remains insufficiently explored in both theory and practice, underscoring its ongoing relevance. The aim of this study is to identify the roles of key signaling pathways—transforming growth factor β (TGF-β), phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt), and Wnt/β-catenin—in the inflammatory response, regenerative mechanisms, and healing processes of soft tissue damage and trophic ulcers in experimental animals and patients with type II diabetes. Materials and Methods. This study is based on an analysis of current scientific literature that addresses this topic. Results. It has been found out that changes in the content and activity of key molecules of signaling pathways lead to disruption of carbohydrate homeostasis and the occurrence of structural and functional dysfunction in damaged tissues against the background of type II diabetes. These include TGF-β, PI3K, Akt and β-catenin. Analysis of experimental data demonstrated that both under the conditions of type II diabetes development and in the occurrence of chronic ulcers of the lower extremities, against the background of this endocrine disease, there is an increase in the level of TGF-β. At the same time the activity of the PI3K/Akt signaling pathway in the above-mentioned studied groups was reduced. The relationship between the development of type II diabetes and the Wnt/β-catenin signaling pathway has been established. Suppression of its activity was accompanied by impaired regeneration of chronic trophic ulcers in type II diabetes. Conclusion. Thus, the mechanism of type II diabetes and chronic peptic ulcer disease, in the same pathology, is associated with a impaired activity of signaling cascades. This concerns the following cellular systems such as TGF-β, PI3K/Akt and Wnt/β-catenin. They can be considered as potential therapeutic targets for the development of newest methods for the treatment of chronic trophic ulcers in type II diabetes in order to accelerate the recovery process of volumetric tissue damage of the lower extremities.