The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration

Sachs W
March 1, 2024
Nat Commun
https://pubmed.ncbi.nlm.nih.gov/38429282

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/38429282

Research summary

This study investigates the role of the proteasome in maintaining kidney filtration barrier integrity by modulating endocytosis in glomerular cells. The research explores how proteasomal activity in podocytes and glomerular endothelial cells affects endocytic processes essential for kidney function.

Key outcome of the study

Endothelial cell-specific deletion of β5i led to morphological alterations in the glomerular filtration barrier, including loss of endothelial fenestrations and podocyte foot process effacement. These structural changes were associated with impaired endocytic activity, resulting in proteinuria and glomerular immunoglobulin deposition.

Mouse model

The study utilized a tamoxifen-inducible, endothelial cell-specific Lmp7 (β5i) Knockout mouse model. This model was generated by crossing mice expressing Cre recombinase under an endothelial-specific promoter with mice harboring floxed Lmp7 alleles, allowing for conditional deletion of the immunoproteasome subunit β5i in endothelial cells upon tamoxifen administration.

TARGET:
Lmp7
Psmb8, β5i, Proteasome subunit beta type-8

Keywords

Nephrology, Glomerular filtration, Endocytosis, Proteasome function, Kidney disease

Technical specifications

Tamoxifen-inducible Knockout, Endothelial cell-specific deletion, Cre-loxP system, Immunoproteasome, Glomerular endothelial cells

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Tissue-specific KO mouse

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