Human kidney organoids produce functional renin.


Journal

Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470

Informations de publication

Date de publication:
01 2021
Historique:
received: 03 04 2020
revised: 29 07 2020
accepted: 10 08 2020
pubmed: 13 9 2020
medline: 22 6 2021
entrez: 12 9 2020
Statut: ppublish

Résumé

Renin production by the kidney is of vital importance for salt, volume, and blood pressure homeostasis. The lack of human models hampers investigation into the regulation of renin and its relevance for kidney physiology. To develop such a model, we used human induced pluripotent stem cell-derived kidney organoids to study the role of renin and the renin-angiotensin system in the kidney. Extensive characterization of the kidney organoids revealed kidney-specific cell populations consisting of podocytes, proximal and distal tubular cells, stromal cells and endothelial cells. We examined the presence of various components of the renin-angiotensin system such as angiotensin II receptors, angiotensinogen, and angiotensin-converting enzymes 1 and 2. We identified by single-cell sequencing, immunohistochemistry, and functional assays that cyclic AMP stimulation induces a subset of pericytes to increase the synthesis and secretion of enzymatically active renin. Renin production by the organoids was responsive to regulation by parathyroid hormone. Subcutaneously implanted kidney organoids in immunodeficient IL2Ry

Identifiants

pubmed: 32918942
pii: S0085-2538(20)30968-6
doi: 10.1016/j.kint.2020.08.008
pii:
doi:

Substances chimiques

Angiotensinogen 11002-13-4
Angiotensin II 11128-99-7
Renin EC 3.4.23.15

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

134-147

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Auteurs

Anusha S Shankar (AS)

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: a.shankar@erasmusmc.nl.

Zhaoyu Du (Z)

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Hector Tejeda Mora (HT)

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Thierry P P van den Bosch (TPP)

Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Sander S Korevaar (SS)

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Ingrid M Van den Berg-Garrelds (IM)

Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Eric Bindels (E)

Department of Haematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Carmen Lopez-Iglesias (C)

Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, The Netherlands.

Marian C Clahsen-van Groningen (MC)

Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Joost Gribnau (J)

Department of Developmental Biology and iPS Core Facility, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Carla C Baan (CC)

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

A H Jan Danser (AHJ)

Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Ewout J Hoorn (EJ)

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Martin J Hoogduijn (MJ)

Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

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Classifications MeSH