Ferroptosis: an important player in the inflammatory response in diabetic nephropathy.

Diabetic nephropathy (DN) is a chronic inflammatory disease that affects millions of diabetic patients worldwide. The key to treating of DN is early diagnosis and prevention. Once the patient enters the clinical proteinuria stage, renal damage is difficult to reverse. Therefore, developing early treatment methods is critical. DN pathogenesis results from various factors, among which the immune response and inflammation play major roles. Ferroptosis is a newly discovered type of programmed cell death characterized by iron-dependent lipid peroxidation and excessive ROS production. Recent studies have demonstrated that inflammation activation is closely related to the occurrence and development of ferroptosis. Moreover, hyperglycemia induces iron overload, lipid peroxidation, oxidative stress, inflammation, and renal fibrosis, all of which are related to DN pathogenesis, indicating that ferroptosis plays a key role in the development of DN. Therefore, this review focuses on the regulatory mechanisms of ferroptosis, and the mutual regulatory processes involved in the occurrence and development of DN and inflammation. By discussing and analyzing the relationship between ferroptosis and inflammation in the occurrence and development of DN, we can deepen our understanding of DN pathogenesis and develop new therapeutics targeting ferroptosis or inflammation-related regulatory mechanisms for patients with DN.

Circular RNAs: An emerging precise weapon for diabetic nephropathy diagnosis and therapy.

Diabetic nephropathy (DN) is a prevalent chronic microvascular complication associated with diabetes mellitus and represents a major cause of chronic kidney disease and renal failure. Current treatment strategies for DN primarily focus on symptom alleviation, lacking effective approaches to halt or reverse DN progression. Circular RNA (circRNA), characterized by a closed-loop structure, has emerged as a novel non-coding RNA regulator of gene expression, attributed to its conservation, stability, specificity, and multifunctionality. Dysregulation of circRNA expression is closely associated with DN progression, whereby circRNA impacts kidney cell injury by modulating cell cycle, differentiation, cell death, as well as influencing the release of inflammatory factors and stromal fibronectin expression. Consequently, circRNA is considered a predictive biomarker and a potential therapeutic target for DN. This review provides an overview of the latest research progress in the classification, functions, monitoring methods, and databases related to circRNA. The paper focuses on elucidating the impact and underlying mechanisms of circRNA on kidney cells under diabetic conditions, aiming to offer novel insights into the prevention, diagnosis, and treatment of DN.

Research progress on multiple cell death pathways of podocytes in diabetic kidney disease.

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and its clinical manifestations are progressive proteinuria, decreased glomerular filtration rate, and renal failure. The injury and death of glomerular podocytes are the keys to DKD. Currently, a variety of cell death modes have been identified in podocytes, including apoptosis, autophagy, endoplasmic reticulum (ER) stress, pyroptosis, necroptosis, ferroptosis, mitotic catastrophe, etc. The signaling pathways leading to these cell death processes are interconnected and can be activated simultaneously or in parallel. They are essential for cell survival and death that determine the fate of cells. With the deepening of the research on the mechanism of cell death, more and more researchers have devoted their attention to the underlying pathologic research and the drug therapy research of DKD. In this paper, we discussed the podocyte physiologic role and DKD processes. We also provide an overview of the types and specific mechanisms involved in each type of cell death in DKD, as well as related targeted therapy methods and drugs are reviewed. In the last part we discuss the complexity and potential crosstalk between various modes of cell death, which will help improve the understanding of podocyte death and lay a foundation for new and ideal targeted therapy strategies for DKD treatment in the future.