Novel parietal epithelial cell subpopulations contribute to focal segmental glomerulosclerosis and glomerular tip lesions.
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Bowman Capsule
/ cytology
Disease Models, Animal
Epithelial Cells
/ metabolism
Female
Glomerulosclerosis, Focal Segmental
/ pathology
Humans
Hyaluronan Receptors
/ metabolism
Ki-67 Antigen
/ metabolism
Kidney Glomerulus
/ pathology
Kidney Tubules, Proximal
/ cytology
Male
Mice
Mice, Transgenic
Middle Aged
PAX8 Transcription Factor
/ genetics
Young Adult
Columbia classification
FSGS
glomerular disease
parietal epithelial cells
tip lesions
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
22
04
2018
revised:
23
01
2019
accepted:
31
01
2019
pubmed:
29
4
2019
medline:
22
9
2020
entrez:
29
4
2019
Statut:
ppublish
Résumé
Beside the classical flat parietal epithelial cells (PECs), we investigated proximal tubular epithelial-like cells, a neglected subgroup of PECs. These cells, termed cuboidal PECs, make up the most proximal part of the proximal tubule and may also line parts of Bowman's capsule. Additionally, a third intermediate PEC subgroup was identified at the junction between the flat and cuboidal PEC subgroups at the tubular orifice. The transgenic mouse line PEC-rtTA labeled all three PEC subgroups. Here we show that the inducible Pax8-rtTA mouse line specifically labeled only cuboidal and intermediate PECs, but not flat PECs. In aging Pax8-rtTA mice, cell fate mapping showed no evidence for significant transdifferentiation from flat PECs to cuboidal or intermediate PECs or vice versa. In murine glomerular disease models of crescentic glomerulonephritis, and focal segmental glomerulosclerosis (FSGS), intermediate PECs became more numerous. These intermediate PECs preferentially expressed activation markers CD44 and Ki-67, suggesting that this subgroup of PECs was activated more easily than the classical flat PECs. In mice with FSGS, cuboidal and intermediate PECs formed sclerotic lesions. In patients with FSGS, cells forming the tip lesions expressed markers of intermediate PECs. These novel PEC subgroups form sclerotic lesions and were more prone to cellular activation compared to the classical flat PECs in disease. Thus, colonization of Bowman's capsule by cuboidal PECs may predispose to lesion formation and chronic kidney disease. We propose that tip lesions originate from this novel subgroup of PECs in patients with FSGS.
Identifiants
pubmed: 31029503
pii: S0085-2538(19)30186-3
doi: 10.1016/j.kint.2019.01.037
pmc: PMC7292612
mid: NIHMS1587676
pii:
doi:
Substances chimiques
CD44 protein, human
0
Cd44 protein, mouse
0
Hyaluronan Receptors
0
Ki-67 Antigen
0
MKI67 protein, human
0
Mki67 protein, mouse
0
PAX8 Transcription Factor
0
Pax8 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
80-93Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK056942
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK080095
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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