PUBLICATION
Autoantibodies Targeting Proteasome Subunit Alpha Type 1 in Autoimmune Podocytopathies
- Authors
- Liu, H., Zhou, C., Wang, D., Meng, H., Zhu, S., Zhang, J., Mao, J., Ye, Q.
- ID
- ZDB-PUB-241011-4
- Date
- 2024
- Source
- Journal of the American Society of Nephrology : JASN 36: 406-419 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 39382973 Full text @ J. Am. Soc. Nephrol.
Citation
Liu, H., Zhou, C., Wang, D., Meng, H., Zhu, S., Zhang, J., Mao, J., Ye, Q. (2024) Autoantibodies Targeting Proteasome Subunit Alpha Type 1 in Autoimmune Podocytopathies. Journal of the American Society of Nephrology : JASN. 36:406-419.
Abstract
Background The antibody against proteasome subunit alpha type 1 (PSMA1) is a podocyte autoantibody in idiopathic nephrotic syndrome (INS) children identified in our previous study. The aim of this study was to explore the characteristics of INS in children and the mechanism underlying its involvement in the development of INS.
Methods The levels of serum anti-PSMA1 autoantibodies in children were detected via protein microarray and compared among different disease groups. The recombinant PSMA1 protein was injected subcutaneously and intraperitoneally into mice to observe glomerular morphology and function. The PSMA1-knockdown and PSMA1-overexpressing cell lines were constructed from mouse podocytes, and their cytoskeleton and function were analyzed. Homozygous zebrafish with psma1 knockout were observed.
Results The levels of serum anti-PSMA1 autoantibodies were higher in INS children and varied with urinary protein. In mice immunized with PSMA1, the presence of serum anti-PSMA1 autoantibody caused albuminuria and damage to the glomerular filtration membrane. Deficiency of PSMA1 impaired the podocyte cytoskeleton and physiological function. Complete deletion of psma1 caused edema, abnormal glomerular morphology and effacement of foot processes in zebrafish.
Conclusions PSMA1 played an important role in the maintenance of podocyte morphology and function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping