iPSC-derived type IV collagen α5-expressing kidney organoids model Alport syndrome.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
28 Sep 2023
28 Sep 2023
Historique:
received:
27
08
2022
accepted:
02
08
2023
medline:
20
11
2023
pubmed:
29
9
2023
entrez:
28
9
2023
Statut:
epublish
Résumé
Alport syndrome (AS) is a hereditary glomerulonephritis caused by COL4A3, COL4A4 or COL4A5 gene mutations and characterized by abnormalities of glomerular basement membranes (GBMs). Due to a lack of curative treatments, the condition proceeds to end-stage renal disease even in adolescents. Hampering drug discovery is the absence of effective in vitro methods for testing the restoration of normal GBMs. Here, we aimed to develop kidney organoid models from AS patient iPSCs for this purpose. We established iPSC-derived collagen α5(IV)-expressing kidney organoids and confirmed that kidney organoids from COL4A5 mutation-corrected iPSCs restore collagen α5(IV) protein expression. Importantly, our model recapitulates the differences in collagen composition between iPSC-derived kidney organoids from mild and severe AS cases. Furthermore, we demonstrate that a chemical chaperone, 4-phenyl butyric acid, has the potential to correct GBM abnormalities in kidney organoids showing mild AS phenotypes. This iPSC-derived kidney organoid model will contribute to drug discovery for AS.
Identifiants
pubmed: 37770589
doi: 10.1038/s42003-023-05203-4
pii: 10.1038/s42003-023-05203-4
pmc: PMC10539496
doi:
Substances chimiques
Collagen Type IV
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
854Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23bm1123002
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP22bm0804013
Informations de copyright
© 2023. The Author(s).
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