Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies
Background: Emerging evidence suggests that autoantibodies targeting podocytes are potential contributors to idiopathic nephrotic syndrome (INS); however, the specific mechanisms remain unclear. This study aims to explore the pathogenic role and underlying mechanisms of anti-vinculin autoantibodies...
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0722 |
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| author | Hanyan Meng Dongjie Wang Chen Zheng Chao Zhou Xinrui Mao Jinglan Gu Xiaohui Qiao Fei Liu Jingjing Wang Haidong Fu Jianhua Mao Qing Ye |
| author_facet | Hanyan Meng Dongjie Wang Chen Zheng Chao Zhou Xinrui Mao Jinglan Gu Xiaohui Qiao Fei Liu Jingjing Wang Haidong Fu Jianhua Mao Qing Ye |
| author_sort | Hanyan Meng |
| collection | DOAJ |
| description | Background: Emerging evidence suggests that autoantibodies targeting podocytes are potential contributors to idiopathic nephrotic syndrome (INS); however, the specific mechanisms remain unclear. This study aims to explore the pathogenic role and underlying mechanisms of anti-vinculin autoantibodies in INS. Methods: Serum anti-vinculin autoantibody levels detected by protein microarray and clinical data were compared among INS patients (n = 147), healthy individuals (n = 84), and patients with other kidney or immune diseases (n = 100 of each disease). Immune-mediated mouse models were established to verify the pathogenicity of anti-vinculin autoantibodies. Mouse urine was monitored for urine protein levels, while immunofluorescence, pathological staining, and electron microscopy assessed kidney pathological and ultrastructural changes. Transcriptome sequencing of mouse kidney tissues was performed to investigate the key molecular mechanisms and signaling pathways involved in kidney injury post-immunization. Results: Anti-vinculin autoantibody levels were specifically elevated in INS patients, with a 54.42% positivity rate, correlating with urinary albumin, serum albumin, cholesterol, and CD19 levels. The average anti-vinculin autoantibody levels dropped markedly in pediatric INS patients during remission. Mouse experiments revealed that injecting anti-vinculin antibodies or recombinant vinculin protein induced proteinuria and podocyte injury in the immunized mice, and the renal phenotype closely resembled the pathological characteristics of minimal change disease. Transcriptome sequencing of renal tissues revealed up-regulation of inflammation, immune responses, cytokine activities, and B cell activation pathways in the immunized mice, while cytoskeleton-related functions were down-regulated. Conclusions: Autoantibodies targeting vinculin act as pathogenic autoantibodies in INS and hold potential value for diagnosing and monitoring INS progression. |
| format | Article |
| id | doaj-art-d09fc205af8249b1b2ad72f395d4f765 |
| institution | OA Journals |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
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| series | Research |
| spelling | doaj-art-d09fc205af8249b1b2ad72f395d4f7652025-08-20T02:32:00ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0722Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune PodocytopathiesHanyan Meng0Dongjie Wang1Chen Zheng2Chao Zhou3Xinrui Mao4Jinglan Gu5Xiaohui Qiao6Fei Liu7Jingjing Wang8Haidong Fu9Jianhua Mao10Qing Ye11Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Women and Children’s Hospital of Ningbo University, Ningbo 315000, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Nephrology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Department of Laboratory Medicine, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou 310052, China.Background: Emerging evidence suggests that autoantibodies targeting podocytes are potential contributors to idiopathic nephrotic syndrome (INS); however, the specific mechanisms remain unclear. This study aims to explore the pathogenic role and underlying mechanisms of anti-vinculin autoantibodies in INS. Methods: Serum anti-vinculin autoantibody levels detected by protein microarray and clinical data were compared among INS patients (n = 147), healthy individuals (n = 84), and patients with other kidney or immune diseases (n = 100 of each disease). Immune-mediated mouse models were established to verify the pathogenicity of anti-vinculin autoantibodies. Mouse urine was monitored for urine protein levels, while immunofluorescence, pathological staining, and electron microscopy assessed kidney pathological and ultrastructural changes. Transcriptome sequencing of mouse kidney tissues was performed to investigate the key molecular mechanisms and signaling pathways involved in kidney injury post-immunization. Results: Anti-vinculin autoantibody levels were specifically elevated in INS patients, with a 54.42% positivity rate, correlating with urinary albumin, serum albumin, cholesterol, and CD19 levels. The average anti-vinculin autoantibody levels dropped markedly in pediatric INS patients during remission. Mouse experiments revealed that injecting anti-vinculin antibodies or recombinant vinculin protein induced proteinuria and podocyte injury in the immunized mice, and the renal phenotype closely resembled the pathological characteristics of minimal change disease. Transcriptome sequencing of renal tissues revealed up-regulation of inflammation, immune responses, cytokine activities, and B cell activation pathways in the immunized mice, while cytoskeleton-related functions were down-regulated. Conclusions: Autoantibodies targeting vinculin act as pathogenic autoantibodies in INS and hold potential value for diagnosing and monitoring INS progression.https://spj.science.org/doi/10.34133/research.0722 |
| spellingShingle | Hanyan Meng Dongjie Wang Chen Zheng Chao Zhou Xinrui Mao Jinglan Gu Xiaohui Qiao Fei Liu Jingjing Wang Haidong Fu Jianhua Mao Qing Ye Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies Research |
| title | Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies |
| title_full | Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies |
| title_fullStr | Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies |
| title_full_unstemmed | Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies |
| title_short | Autoantibodies Targeting Vinculin Reveal Novel Insight into the Mechanisms of Autoimmune Podocytopathies |
| title_sort | autoantibodies targeting vinculin reveal novel insight into the mechanisms of autoimmune podocytopathies |
| url | https://spj.science.org/doi/10.34133/research.0722 |
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