Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis

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Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis

Basic Research | 更新时间：2024-02-19

- Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 44, Issue 2, Pages: 254-261(2023)
- 作者机构：
  
  1.东莞市人民医院肾内科，广东东莞，523059
  2.中山大学附属第一医院风湿免疫科，广东广州，510080
- 作者简介：
  
  GUO Chao-huan； E-mail： guochh9@mail.sysu.edu.cn
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0209
  CLC： R59
- Received：03 November 2022，
  
  Published：20 March 2023
- 稿件说明：
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胡浩强,李梦圆,杨念生等.suPAR在原发性局灶节段性肾小球硬化足细胞损伤的作用[J].中山大学学报（医学科学版）,2023,44(02):254-261.

HU Hao-qiang,LI Meng-yuan,YANG Nian-sheng,et al.Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(02):254-261.
胡浩强,李梦圆,杨念生等.suPAR在原发性局灶节段性肾小球硬化足细胞损伤的作用[J].中山大学学报（医学科学版）,2023,44(02):254-261. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0209.

HU Hao-qiang,LI Meng-yuan,YANG Nian-sheng,et al.Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(02):254-261. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0209.

摘要

目的

2

探讨suPAR在原发性FSGS患者足细胞损伤中的作用。

方法

2

①收集原发性FSGS患者（17 例）血清，以健康志愿者（10 例）及其他类型原发性肾病综合征患者（10 例）作为正常及疾病对照，采用ELISA检测suPAR水平；②采用suPAR体外刺激足细胞，收集细胞行流式细胞术分析细胞凋亡情况；收集细胞，提取RNA，行RNAseq；③足细胞RNAseq数据差异基因筛选，上下调基因行KEGG及GO通路富集分析，热图展示足细胞局部黏附、滤过膜、细胞骨架及内吞相关基因变化情况，并行qPCR验证。

结果

2

①FSGS患者suPAR水平显著升高，且其他肾病综合征（NS）患者suPAR水平显著升高；②suPAR刺激显著改变人足细胞转录组，共筛选出272 个上调基因和288 个下调基因；③上下调基因分别行KEGG和GO通路富集分析发现focal adhesion及DNA复制及损伤修复相关通路显著下调；④suPAR未显著增加足细胞凋亡。

结论

2

原发性FSGS患者suPAR水平显著升高；suPAR可能通过干扰基因组稳态，破坏足细胞局部黏附、滤过膜及细胞骨架相关功能分子促进足细胞损伤。

Abstract

Objective

2

This study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS.

Methods

2

① The sera of primary FSGS patients （17 cases） were collected. Healthy volunteers （10 cases） and patients with other types of primary nephrotic syndrome （10 cases） were set as normal and disease controls. SuPAR levels were detected by ELISA； ② Podocytes were stimulated by suPAR in vitro， and cells were collected to analyze apoptosis by flow cytometry and for RNAseq analysis； ③ Differentially expressed genes （DEGs） were screened from RNAseq data. Both up-regulated and down-regulated genes were analyzed by KEGG and GO enrichment analysis. Heat map was used to show expression of genes related to podocyte focal adhesion， slit diaphragm and actin dynamics and endocytosis. Differentially expressed genes were verified by qPCR.

Results

2

① The level of suPAR in FSGS patients was significantly increased， and that in other nephrotic syndrome（NS） patients was also significantly increased； ② suPAR stimulation significantly altered the transcriptome pattern of human podocytes. A total of 272 up-regulated genes and 288 down-regulated genes were screened； ③ KEGG and GO enrichment analysis of up-regulated and down-regulated genes showed that Focal adhesion and DNA replication and DNA repair related pathways were significantly down-regulated； ④ suPAR did not increase podocyte apoptosis.

Conclusion

2

The level of suPAR is significantly increased in patients with primary FSGS. SuPAR may promote podocyte injury by interfering with genomic homeostasis and disrupting focal adhesion， slit diaphragm， actin dynamics and endocytosis-related functional molecules of podocytes.

关键词

Keywords

references

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陈婧，黄泽宇，周学东，等 . CD47分子相关信号通路及CD47在病原感染中的研究进展［J］. 四川大学学报（医学版）， 2022 ， 53 （ 3 ）： 523 - 527 .

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Wei C ， Trachtman H ， Li J ， et al . Circulating suPAR in two cohorts of primary FSGS ［J］. J Am Soc Nephrol ， 2012 ， 23 （ 12 ）： 2051 - 2059 .

Huang J ， Liu G ， Zhang YM ， et al . Urinary soluble urokinase receptor levels are elevated and pathogenic in patients with primary focal segmental glomerulosclerosis ［J］. BMC Med ， 2014 ， 12 ： 81 .

Alachkar N ， Wei C ， Arend LJ ， et al . Podocyte effacement closely links to suPAR levels at time of posttransplantation focal segmental glomerulosclerosis occurrence and improves with therapy ［J］. Transplantation ， 2013 ， 96 （ 7 ）： 649 - 656 .

Cathelin D ， Placier S ， Ploug M ， et al . Administration of recombinant soluble urokinase receptor per se is not sufficient to induce podocyte alterations and proteinuria in mice ［J］. J Am Soc Nephrol ， 2014 ， 25 （ 8 ）： 1662 - 1668 .

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