Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis.
Animals
Capillaries
Disease Models, Animal
Disease Progression
Fluorescence
Fluorescent Dyes
/ chemistry
Genes, Reporter
/ genetics
Glomerulonephritis
/ immunology
Green Fluorescent Proteins
/ chemistry
Histocytological Preparation Techniques
/ methods
Humans
Imaging, Three-Dimensional
Male
Mice
Mice, Transgenic
Microscopy, Electron, Transmission
Podocytes
/ physiology
Single-Cell Analysis
/ methods
computational analysis
crescentic nephritis
optical clearing
parietal cell activation
podocyte loss
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
06
10
2018
revised:
23
01
2019
accepted:
28
02
2019
pubmed:
4
6
2019
medline:
2
10
2020
entrez:
4
6
2019
Statut:
ppublish
Résumé
Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hypercellular lesions and the rapid loss of kidney function induced by nephrotoxic serum. Results show a graded susceptibility of the glomeruli, significant podocyte loss and capillary injury. These effects are associated with activation of parietal epithelial cells and formation of glomerular lesions that may evolve and obstruct the kidney tubule, thereby explaining the loss of kidney function. Thus, our work provides new high-throughput endpoints for the analysis of complex tissues with single-cell resolution.
Identifiants
pubmed: 31155155
pii: S0085-2538(19)30318-7
doi: 10.1016/j.kint.2019.02.034
pii:
doi:
Substances chimiques
Fluorescent Dyes
0
enhanced green fluorescent protein
0
Green Fluorescent Proteins
147336-22-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
505-516Informations de copyright
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.