Hushmandi Kiavash, Klionsky Daniel J, Farahani Najma, Reiter Russel J, Imani Fooladi Abbas Ali Imani, Alimohammadi Mina, Aref Amir Reza
Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Clin Exp Med. 2025 Jun 18;25(1):208. doi: 10.1007/s10238-025-01740-w.
Diabetic nephropathy (DN) is a major complication of diabetes mellitus, predominantly affecting the kidneys of diabetic patients and resulting in increased morbidity and mortality. Current standard treatments for diabetes have proven insufficient in halting the progression of DN, highlighting the urgent need for innovative and more effective therapeutic strategies. Pyroptosis, a pro-inflammatory regulated cell death process, has been previously associated with DN development. Recent evidence indicates that the NLRP3 inflammasome, a key inflammatory pathway complex, promotes DN through pyroptosis. Consequently, inhibiting inflammasome activity has emerged as a promising therapeutic target against DN, in conjunction with pyroptosis. This review introduces non-coding RNAs (ncRNAs), particularly circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), as potential regulators of pyroptosis in DN, as recent studies have documented their dysregulation in DN pathogenesis. In this study, we aim to discuss the characteristics of lncRNAs, circRNAs, and pyroptosis and explore their potential interconnection in DN development. By elucidating the link between these RNA molecules and pyroptosis, our goal is to deepen our understanding of the underlying mechanisms of the disease. This knowledge could lead to the identification of new therapeutic targets and the development of innovative treatments for DN by modulating pyroptosis.
糖尿病肾病(DN)是糖尿病的一种主要并发症,主要影响糖尿病患者的肾脏,并导致发病率和死亡率增加。目前的糖尿病标准治疗方法已被证明不足以阻止DN的进展,这凸显了对创新且更有效治疗策略的迫切需求。细胞焦亡是一种促炎性调节性细胞死亡过程,此前已被认为与DN的发生有关。最近的证据表明,NLRP3炎性小体作为关键的炎症信号通路复合体,通过细胞焦亡促进DN的发生。因此,抑制炎性小体活性已成为与细胞焦亡相关的、有前景的DN治疗靶点。本综述介绍了非编码RNA(ncRNA),特别是环状RNA(circRNA)和长链非编码RNA(lncRNA),作为DN中细胞焦亡的潜在调节因子,因为最近的研究记录了它们在DN发病机制中的失调。在本研究中,我们旨在讨论lncRNA、circRNA和细胞焦亡的特征,并探索它们在DN发生发展中的潜在联系。通过阐明这些RNA分子与细胞焦亡之间的联系,我们的目标是加深对该疾病潜在机制的理解。这些知识可能会通过调节细胞焦亡来识别新的治疗靶点,并开发出针对DN的创新治疗方法。