Iizuka Yusuke, Sasaki Masanori, Terada Kojiro, Sakai Takuro, Nagaoka Yoshinobu, Fukumura Shinobu, Kocsis Jeffery D, Tsugawa Takeshi, Honmou Osamu
Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan.
Department of Neural Regenerative Medicine, Institute of Regenerative Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan.
Pathophysiology. 2025 May 1;32(2):19. doi: 10.3390/pathophysiology32020019.
Podocytes are essential for kidney function, and their dysfunction can result in nephrotic syndrome, such as minimal change disease (MCD). Oxidative stress contributes to podocyte damage. We investigated the therapeutic potential of intravenously infused mesenchymal stem cells (MSCs) in a puromycin aminonucleoside (PAN)-induced rodent MCD model, focusing on oxidative stress modulation. Sprague-Dawley rats were divided into three groups: intact, PAN-Vehicle, and PAN-MSC. MCD was induced through subcutaneous PAN injection. MSCs were infused intravenously in the PAN-MSC group on day 7. Urinary albumin, serum albumin, and creatinine levels were assessed. Histological analysis of the renal cortex was performed. Podocyte protein (NPHS1, NPHS2, and PODXL) and antioxidant enzyme (SOD1, SOD2, and GPX1) levels were measured using quantitative real-time reverse-transcription PCR (qRT-PCR). MSC infusion significantly reduced proteinuria and restored podocyte structure in the PAN-MSC group. Electron microscopy revealed that infused MSCs could inhibit the fusion of the foot process induced by PAN injection. qRT-PCR showed that intravenous infusion of MSCs rescued the inhibition of GPX1 expression. GFP-labeled MSCs accumulated at the podocyte injury sites. Systemic MSC infusion mitigates PAN-induced MCD by reducing proteinuria, preserving podocyte structure, and modulating oxidative stress via the GPX1 pathway, offering a potential therapeutic approach for nephrotic syndrome.
足细胞对肾脏功能至关重要，其功能障碍可导致肾病综合征，如微小病变病（MCD）。氧化应激会导致足细胞损伤。我们研究了静脉输注间充质干细胞（MSCs）在嘌呤霉素氨基核苷（PAN）诱导的啮齿动物MCD模型中的治疗潜力，重点关注氧化应激调节。将Sprague-Dawley大鼠分为三组：完整组、PAN-载体组和PAN-MSC组。通过皮下注射PAN诱导MCD。在第7天对PAN-MSC组静脉输注MSCs。评估尿白蛋白、血清白蛋白和肌酐水平。对肾皮质进行组织学分析。使用定量实时逆转录PCR（qRT-PCR）测量足细胞蛋白（NPHS1、NPHS2和PODXL）和抗氧化酶（SOD1、SOD2和GPX1）水平。在PAN-MSC组中，输注MSCs显著降低了蛋白尿并恢复了足细胞结构。电子显微镜显示，输注的MSCs可抑制PAN注射诱导的足突融合。qRT-PCR表明，静脉输注MSCs可挽救GPX1表达的抑制。绿色荧光蛋白标记的MSCs聚集在足细胞损伤部位。全身输注MSCs通过减少蛋白尿、保留足细胞结构以及通过GPX1途径调节氧化应激来减轻PAN诱导的MCD，为肾病综合征提供了一种潜在的治疗方法。
