Chronic kidney disease affects about 10% of the world’s population (CKD). End-stage renal disease (ESRD), which necessitates dialysis or kidney transplantation, has an extremely high chance of developing from chronic kidney disease (CKD). There is no effective treatment for CKD at the moment.
Thus, it is crucial to identify the underlying pathogenic mechanisms of CKD in order to develop efficient treatment plans that can both prevent and treat the condition. DNA-PKcs may be a viable target for the treatment of CKD, according to a recent Nature Communications study. Renal interstitial fibrosis, which is linked to an atypical expression of profibrotic proteins such transforming growth factor-beta 1 (TGF-1)-induced myofibroblast activation and epithelial dedifferentiation, is a significant pathogenic feature of CKD. The activation of TGF-1 has a crucial role in interstitial fibrosis.
When studying the relationship between metabolic dysregulation and interstitial fibrosis, researchers saw that myofibroblasts and renal tubular epithelial cells, which make up kidney tissue, underwent metabolic reprogramming. This event affects how CKD develops.
There is a considerable decrease in fatty acid oxidation (FAO) and a metabolic switch to glycolysis when kidney cells undergo metabolic reprogramming. Interstitial fibrosis and immune cell infiltration are the results of these symptoms. Many animal models of renal fibrosis have demonstrated that fibrosis can be reduced by pharmacological or genetic methods that block glycolysis and restore FAO.
Reactive oxygen species (ROS) or DNA double-strand breaks can activate the trimeric complex made up of a catalytic subunit (DNA-PKcs) and a Ku70/80 heterodimer known as DNA-dependent protein kinase (DNA-PK) (DSBs). Facilitating nonhomologous
