Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Basic Medical Research Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Children Genitourinary Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Structural Malformations in Children of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Chem Biol Interact. 2023 Sep 1;382:110559. doi: 10.1016/j.cbi.2023.110559. Epub 2023 May 27.
Nephrotic syndrome (NS) is a chronic kidney disease mainly caused by impaired podocytes, ultimately resulting in massive proteinuria or even end-stage renal disease (ESRD).
The objective of this study was to explore the potential pathogenesis of NS caused by podocyte injury, and further explore the underlying mechanism through data mining, bioinformatics analysis, and experimental verification. The integrated analyses including Seurat, CellChat, gene ontology (GO), and molecular docking were performed based on the single-cell RNA-seq data (scRNA-seq). The adriamycin (ADR)-induced podocyte injury model in vitro was established to conduct the experimental verification for bioinformatics analysis results through western blot and real-time quantitative PCR (RT-qPCR).
The results of bioinformatics analysis revealed that the bone morphogenetic protein (BMP) signaling pathway was involved in the podocyte-to-podocyte communication, which plays a crucial role in podocyte injury. The expression of BMP7 was significantly increased in ADR-induced podocytes through activating the Adenosine-monophosphate activated-protein kinase/Mammalian target of rapamycin (AMPK/mTOR) mediated autophagy pathway, and these findings were confirmed by in vitro experiments.
This study first demonstrated that BMP7 participated in ADR-induced podocyte injury. The BMP7/AMPK/mTOR mediated autophagy pathway may play a crucial role in podocyte injury, which may be the potential therapeutic target for NS patients.
肾病综合征（NS）是一种主要由足细胞损伤引起的慢性肾脏疾病，最终导致大量蛋白尿，甚至终末期肾病（ESRD）。
本研究旨在探讨足细胞损伤导致 NS 的潜在发病机制，并通过数据挖掘、生物信息学分析和实验验证进一步探讨其潜在机制。基于单细胞 RNA 测序数据（scRNA-seq），进行了包括 Seurat、CellChat、基因本体（GO）和分子对接在内的综合分析。通过 Western blot 和实时定量 PCR（RT-qPCR），建立阿霉素（ADR）诱导的足细胞损伤模型，对生物信息学分析结果进行实验验证。
生物信息学分析结果表明，骨形态发生蛋白（BMP）信号通路参与了足细胞间的通讯，在足细胞损伤中起关键作用。通过激活腺苷酸单磷酸激活蛋白激酶/雷帕霉素靶蛋白（AMPK/mTOR）介导的自噬通路，ADR 诱导的足细胞中 BMP7 的表达显著增加，体外实验也证实了这一点。
本研究首次表明 BMP7 参与了 ADR 诱导的足细胞损伤。BMP7/AMPK/mTOR 介导的自噬通路可能在足细胞损伤中起关键作用，这可能是 NS 患者的潜在治疗靶点。
