Advances in understanding the NLRP3 inflammasome‑mediated mechanisms and therapeutic targets in diabetic nephropathy (Review)

Diabetic nephropathy (DN), a severe microvascular complication of diabetes, has exhibited a steadily increasing global incidence and is a major contributor to diabetes‑related morbidity and mortality. DN is characterized by glomerular sclerosis, podocyte loss, tubular atrophy and excessive extracellular matrix deposition, among other features. The pathogenesis of DN is complex, involving multiple pathological processes, with the inflammatory cascade recognized as the core driver of its progression. Abnormal activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key component of the innate immune system, can trigger pyroptosis and thereby aggravate renal injury. Whilst current literature primarily describes isolated mechanisms of DN, the present review summarizes the pathogenesis of DN and the NLRP3 inflammasome‑related signaling pathways, proposing a novel three‑tier hierarchical regulatory framework (upstream priming, midstream activation and downstream execution) for the five core NLRP3‑related signaling pathways in DN, and systematically dissects the mitochondrial metabolic‑cGAS‑STING synergistic mechanism that drives NLRP3 activation, thus addressing the research gap in metabolic‑immune crosstalk in DN. Furthermore, potential therapeutic agents targeting the NLRP3 inflammasome are discussed, and targeted therapeutic strategies stratified according to in vivo and in vitro validation evidence (such as small‑molecule inhibitors, traditional Chinese medicine monomers/compounds and gene therapy) to provide a clear roadmap to clinical translation. Although current research on DN is limited, the findings and analyses assessed in the present review provide valuable insights into its pathogenesis, treatment, prognosis and directions for future experimental studies.