The Role of Intracellular Signaling Pathways in the Development of Lower Extremity Trophic Pathology and Peculiarities of Its Regeneration in Type 2 Diabetes (Part 2)

Abstract

Introduction. In endocrinological science, the pathogenesis of trophic ulcers in soft tissues, which frequently occur and progress in patients with type 2 diabetes, remains a significant yet underexplored issue. Gaining a deeper understanding of the etiology and development of chronic trophic ulcers in the context of type 2 diabetes is crucial for advancing innovative and highly effective therapeutic approaches in the near future. The aim of this study is to investigate the role of certain “minor” signaling pathways, including hypoxia-inducible factor (HIF), Notch, and nuclear factor E2-related factor 2 (Nrf2), in the regeneration of cellular elements in soft tissue trophic ulcers observed in experimental animals and patients with type 2 diabetes. Material and methods. Based on data from modern professional literature, a study was conducted to elucidate the participation of the НIF-1, Notch and Nrf2 signaling pathways in the development of acute wounds, type 2 diabetes and, finally, the occurrence, progression, and healing of trophic ulcers during this endocrine disease. Results. It has been established that under hypoxic conditions at the initial stage of the inflammatory process during the regeneration of damaged soft tissues, an increase in the НIF-1α content is observed. The involvement of this molecular factor in the development of type 2 diabetes and the suppression of its expression level in chronic trophic ulcers against the background of type 2 diabetes were revealed. It has been demonstrated that another messenger cascade, Notch, is involved in all stages of healing of wound defects of the skin in acute wounds. At the same time, with the progression of type 2 diabetes, as well as the occurrence of chronic trophic ulcers in this endocrinological disease, the activation of this intracellular cascade was recorded. The process of regeneration and healing of damaged soft tissues of the skin was also accompanied by an increase in the content of the Nrf2. However, the development of type 2 diabetes was characterized by a decrease in the level of expression of this molecule. It is important to stress that the role of Nrf2 in the healing of trophic ulcers during type 2 diabetes remains not fully studied. Conclusion. The pathogenesis of chronic trophic ulcers in type 2 diabetes is based on disturbances in the activity of individual intracellular “minor” signaling pathways. Further study of the role of messenger cascades such as НIF-1, Notch and Nrf2 will contribute to the development of new approaches to improving the effectiveness of treatment of patients with chronic trophic ulcers of the lower extremities under type 2 diabetes.