Review the Role of Metabolism Reprogramming in the Pathogenesis of Post-surgical Adhesion: A New Therapeutic Strategy

Abstract

Abstract: Metabolic reprogramming is defined as the skill of cells to change their metabolism to support the induced energy demand due to continuous growth. Metabolic reprogramming is a well- known occurrence in the progression of neoplastic cells, although, evidence has shown that it is present in fibrotic disorders. Post-surgical adhesion as a fibrotic disorder is a medical challenge and is defined by fibrotic bands connected between organs with the abdominal wall. Despite many investigations carried out about the pathogenesis of the disorder but there are many unknowns, therefore, targeting special pathways may have the potential to prevent the formation of fibrotic bands post-operative. Glycolysis is a necessary metabolic pathway in living cells. In hypoxic conditions, it is the dominant pathway in the production of energy for different types of cells such as fibroblasts, immune cells, and endothelial cells. Also, glycolysis is a main downstream target for transforming growth factor β (TGF-β) and upregulates during fibrotic conditions. Furthermore, this is noteworthy that hypoxia induces factor 1 alpha (HIF-1α) as a transcription factor, elevated during the hypoxia condition stimulates different signaling pathways such as TGF-β/SMAD, nuclear factor kappa B (NF-kB), and mTOR pathway to control glycolytic metabolism and T-cell trafficking for immune cell migration. Different evidence has indicated that the administration of glycolytic inhibitors has the potential to prevent the development of fibrotic markers. In this review, we pointed out the role of the glycolysis pathway and its connection to profibrotic cytokines to promote inflammatory and fibrotic pathways. Based on the results of studies related to fibrotic disorders we hypothesized that targeting glycolysis may have therapeutic potential in the prevention of postoperative adhesions.