Yang Qianqian, Xie Wenjia, Wang Xiao, Luo Jing, Zhou Yang, Cao Hongdi, Sun Qi, Jiang Lei, Yang Junwei
Center for Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Front Pharmacol. 2022 Jan 31;12:707006. doi: 10.3389/fphar.2021.707006. eCollection 2021.
Diabetic kidney disease (DKD) is currently one of the leading causes of end-stage renal disease (ESRD). Mitochondrial dysfunction in podocyte is involve in DKD development. However, whether early mitochondrial stabilization delays or reverses DKD progression has not been elucidated. SS31 is a novel tetrapeptide compound that targets the inner mitochondrial membrane and protects mitochondria by reducing ROS and inhibiting cardiolipin oxidation. Our study discovered that SS31 might have a long-term podocyte protection in DKD. In this study, we examined the glomerular pathological damage and proteinuria at different stages of diabetes. Results revealed that podocyte mitochondrial injury appeared at the early stage of DKD. Early treatment with SS31 could protect podocyte and alleviate the development of DKD via inhibiting OMA1-mediated hydrolysis of OPA1. Those data indicate that SS31 might be a promising agent in delaying the development of DKD and OMA1-mediated hydrolysis of OPA1 in mitochondria, and SS31 is a novel therapeutic target for the treatment of DKD.
糖尿病肾病（DKD）是目前终末期肾病（ESRD）的主要病因之一。足细胞中的线粒体功能障碍参与了DKD的发展。然而，早期线粒体稳定是否能延缓或逆转DKD进展尚未阐明。SS31是一种新型四肽化合物，靶向线粒体内膜，通过减少活性氧（ROS）和抑制心磷脂氧化来保护线粒体。我们的研究发现，SS31可能对DKD具有长期的足细胞保护作用。在本研究中，我们检查了糖尿病不同阶段的肾小球病理损伤和蛋白尿。结果显示，足细胞线粒体损伤出现在DKD早期。早期用SS31治疗可通过抑制OMA1介导的OPA1水解来保护足细胞并减轻DKD的发展。这些数据表明，SS31可能是延缓DKD发展以及线粒体中OMA1介导的OPA1水解的有前景的药物，并且SS31是治疗DKD的新治疗靶点。
