Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis

Increasing evidence indicates that regulated cell death (RCD), such as apoptosis, anoikis, autophagy, pyroptosis, necroptosis, ferroptosis and cuproptosis, plays crucial roles in renal tissue injury and the progression of fibrosis by promoting inflammatory responses and extracellular matrix deposition. Therefore, elucidating the molecular mechanisms of different types of RCD is essential for treating patients with renal fibrosis. This review comprehensively presents the distinct and interactive roles of RCD in renal fibrosis pathogenesis and elucidates the crosstalk among different forms of RCD and core fibrotic signaling pathways. Moreover, we analyzed clinically promising RCD-related therapeutic targets and identified future research directions, thereby providing a theoretical basis for the clinical treatment of renal fibrosis patients. To mitigate the threat of compensatory crosstalk between RCD pathways during clinical translation, the development of drugs that simultaneously target multiple forms of RCD may offer a novel approach for precise renal fibrosis treatment.