The Role and Therapeutic Potential of the STING Signaling Pathway in the Pathogenesis of Diabetic Nephropathy

Diabetes mellitus currently represents a major public health burden worldwide. Among diabetic individuals, diabetic nephropathy (DN) is a frequent and serious microvascular complication that markedly affects both patients' quality of life and clinical outcomes. DN has also emerged as the leading contributor to end-stage renal disease (ESRD). Over recent years, the stimulator of interferon genes (STING) signaling pathway (an essential element of the innate immune system) has drawn substantial research interest because of its involvement in inflammation and cell injury. This article reviews the fundamental mechanisms of the STING pathway and its regulatory functions in the pathogenesis of DN, with a focus on how the STING pathway mediates inflammatory responses, apoptosis, and fibrosis in diabetic renal tissues. Additionally, combining the latest findings from preclinical and clinical research, we discuss potential therapeutic strategies targeting the STING pathway. Beyond traditional STING inhibitor therapies, we highlight the emerging field of precision medicine for DN, summarizing recent research achievements in gene intervention, such as CRISPR-based gene editing, RNA interference (RNAi) technologies, and combination therapy strategies. Distinct from prior reviews, this work discusses the emerging concept that STING may function as a molecular hub connecting inflammation, fibrosis, and cell death in DN, while emphasizing that this concept is mainly supported by preclinical and early human observational evidence. Through this comprehensive review, we aim to enhance our understanding of the role of the STING signaling pathway in DN, identify novel therapeutic targets, and provide theoretical perspectives for the prevention and treatment strategies that require further clinical validation.