Abstract: TH-PO559
Proteomic Analysis of Glomerular Extracellular Matrix Suggests a Potential Role of Complement in the Pathogenesis of Idiopathic Collapsing Glomerulopathy Associated with APOL1 High-Risk Genotypes
Session Information
- Glomerular Diseases: Omics, Biomarkers, and Tools
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Neves, Precil D., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Siqueira, Talita Souza, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Feitosa, Valkercyo Araújo, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Watanabe, Andreia, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Watanabe, Elieser H., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Castelli, Jussara Bianchi, Fleury Laboratory, São Paulo, Brazil
- Gonçalves, Natalia Gomes, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Lin, Chin Jia, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Cavalcante, Livia Barreira, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Malheiros, Denise M., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Jorge, Lectícia, Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Noronha, Irene L., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
- Carvalho, Valdemir Melechco, Fleury Laboratory, São Paulo, Brazil
- Onuchic, Luiz F., Universidade de Sao Paulo Faculdade de Medicina, Sao Paulo, São Paulo, Brazil
Background
The pathogenesis of collapsing glomerulopathy (CG), a highly aggressive nephropathy, remains largely unclear. While a significant fraction of idiopathic CG (ICG) cases is associated with APOL1 high-risk genotypes (HRG), the differences in pathogenic processes between ICG associated with HRG (ICG+HRG) and with APOL1 low-risk genotypes (ICG+LRG) are still poorly characterized.
Methods
To identify novel potential differences in molecular pathogenic pathways between ICG+HRG and ICG+LRG, we performed proteomic analyses of glomerular extracellular matrix (ECM) in 4 groups of patients: ICG+HRG (9 cases); non-Mendelian ICG+LRG (8 cases); FSGS-NOS+LRG (5 cases, a disease profile control); and normal kidney tissue (NK, 6 cases, a baseline control obtained from non-affected areas of nephrectomies secondary to malignancy). Glomerular samples were acquired by laser-microdissection. The relative abundance of proteins was compared between groups.
Results
We identified 931 proteins present in at least 60% of the samples of one group. Two hundred of them were classified as ECM proteins. C1QC, CFHR1, and hornerin were detected exclusively in the ICG+HRG group while laminin alpha 2 was detected only in the ICG+LRG group. Moreover, annexin A4, C5, C9, C4b-binding protein alpha chain (C4BPA), Serpin Family B Member 6 (SERPINB6), SERPINB9, and SERPINC1 stood out as displaying greater abundance in ICG+HRG than NK, and C4BPA, COL4A4, COL4A5, laminin beta 2, and nidogen-1 as presenting more abundance in ICG+HRG than FSGS-NOS+LRG. Annexin A4, annexin A6, SERPINB9 and SERPINH1 stood out as displaying greater abundance in ICG+LRG than NK. No difference in abundance was detected between ICG+HRG and ICG+LRG.
Conclusion
Our data showed that ICG+HRG and ICG+LRG presented patterns of glomerular ECM proteins associated with inflammation, immune activation and fibrosis pathways, and suggested a potential involvement of the complement system in the pathogenesis of ICG+HRG.