Role of suPAR in the Pathogenesis of Podocyte Injury of Primary Focal Segmental Glomerulosclerosis
10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0209
- VernacularTitle:suPAR在原发性局灶节段性肾小球硬化足细胞损伤的作用
- Author:
Hao-qiang HU
1
;
Meng-yuan LI
2
;
Nian-sheng YANG
2
;
Chao-huan GUO
2
Author Information
1. Department of Nephrology,Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan People's Hospital),Dongguan,523059
2. Department of Rheumatology,The First Affiliated Hospital, Sun Yat-sen University,Guangzhou,510080
- Publication Type:Journal Article
- Keywords:
suPAR;
focal segmental glomerulosclerosis;
podocyte
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2023;44(2):254-261
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis study aims to investigate the role of suPAR in the pathogenesis of podocyte injury in FSGS. Methods① 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. Results① 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. ConclusionThe 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.