Endoglin promotes podocyte injury and apoptosis through the autophagy-lysosomal pathway in lupus nephritis

被引：0
作者：
Ma, Junxue [1 ,2 ]
You, Yanwu [1 ,3 ]
机构：
[1] Jinan Univ, Affiliated Hosp 1, Dept Nephrol, Guangzhou, Peoples R China
[2] Youjiang Med Univ Nationalities, Affiliated Southwest Hosp, Dept Nephrol, Baise, Peoples R China
[3] Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Nephrol, 6 Taoyuan Rd, Nanning 530000, Peoples R China
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY | 2025年 / 150卷
关键词：
Endoglin; Podocytes; Autophagy-lysosomal pathway; Lupus nephritis;
D O I：
10.1016/j.intimp.2025.114272
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Background: Endoglin (ENG) has emerged as a potential disease biomarker and therapeutic target, yet its role in lupus nephritis (LN) remains underexplored. This study investigated the role of ENG in podocyte injury and apoptosis during the development of LN as well as the related molecular mechanisms. Methods: ENG levels in patient urine samples were measured using ELISA, and disease activity was assessed via SLEDAI-2 K criteria. Podocytes were transfected with ENG siRNA, and downstream differentially expressed proteins were identified using proteomics, followed by KEGG and PPI analyses. ENG, LAMP1, and Nephrin expression was analyzed using western blotting and immunofluorescence. LN-IgG-induced podocytes were treated with a lysosomal inhibitor (leupeptin), followed by functional assays. Transmission electron microscopy was used to observe autolysosomes and apoptotic vesicles. Results: The level of ENG was high in the urine of SLE patients, renal tissues of lupus-prone mice, and LN-IgGinduced podocytes and was positively correlated with the disease activity of patients. In renal tissues of lupusprone mice,the expression of ENG was up-regulated while LAMP1 and Nephrin were down-regulated. Proteomics revealed 289 differentially expressed proteins after ENG knockdown. KEGG and PPI analysis showed significant enrichment of differentially expressed proteins in the lysosomal pathway. After LN-IgG induction, the functions of podocytes change. Knockdown of ENG can alleviate this situation, while lysosomal inhibitors would weaken the alleviating effect. Conclusion: ENG fostered injury and apoptosis of LN-IgG-induced podocytes by negatively regulating the autophagy-lysosomal pathway, implicating ENG as a key regulator and attractive therapeutic target for LN.
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页数：10
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