Agonists of prostaglandin E <sub>2</sub> receptors as potential first in class treatment for nephronophthisis and related ciliopathies-Reference-Cited by-同舟云学术

Agonists of prostaglandin E ₂ receptors as potential first in class treatment for nephronophthisis and related ciliopathies

Published:2022-04-28 Issue:18 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Garcia Hugo¹²,Serafin Alice S.¹^ORCID,Silbermann Flora¹,Porée Esther¹^ORCID,Viau Amandine¹^ORCID,Mahaut Clémentine³,Billot Katy¹,Birgy Éléonore¹,Garfa-Traore Meriem¹,Roy Stéphanie¹^ORCID,Ceccarelli Salomé¹,Mehraz Manon¹,Rodriguez Pamela C.³,Deleglise Bérangère³^ORCID,Furio Laetitia³,Jabot-Hanin Fabienne⁴^ORCID,Cagnard Nicolas⁴,Del Nery Elaine⁵,Fila Marc⁶,Sin-Monnot Soraya³^ORCID,Antignac Corinne¹⁷^ORCID,Lyonnet Stanislas⁷⁸,Krug Pauline⁹,Salomon Rémi¹⁹,Annereau Jean-Philippe³¹⁰^ORCID,Benmerah Alexandre¹^ORCID,Delous Marion¹^ORCID,Briseño-Roa Luis³¹⁰^ORCID,Saunier Sophie¹^ORCID

Affiliation:

1. Laboratory of Hereditary Kidney Disease, Imagine Institute, Université Paris Cité, INSERM UMR 1163, 75015 Paris, France

2. Department of Nephrology, Groupe Hospitalier Sorbonne Université, 75013 Paris, France

3. Alexion R&D France, Imagine Institute, 75015 Paris, France

4. Bioinformatic platform, Imagine Institute, 75015 Paris, France

5. BioPhenics High-Content Screening Laboratory, Cell and Tissue Imaging Facility, Translational Research Department, Institut Curie, Paris Science and Letters Research University, 75248 Paris, France

6. Pediatric Nephrology Unit, Arnaud de Villeneuve Hospital, Montpellier University Hospital, Centre de Référence Maladies Rénales Rares and Institut Genomique Fonctionnelle, INSERM UMR 5203 CNRS U1191, 34000 Montpellier, France

7. Department of Genetics, Necker Hospital, Assistance Publique–Hôpitaux de Paris, 75015 Paris, France

8. Laboratory of Embryology and Genetics of Congenital Malformations, Université Paris Cité, INSERM UMR 1163, 75015 Paris, France

9. Pediatric Nephrology, Necker Enfants Malades, Assistance Publique–Hôpitaux de Paris, Paris, 75015 France

10. Medetia Pharmaceuticals, Imagine Institute, 75015 Paris, France

Abstract

Significance Juvenile nephronophthisis (NPH) is a renal ciliopathy due to a dysfunction of primary cilia for which no curative treatment is available. This paper describes the identification of agonists of prostaglandin E 2 receptors as a potential therapeutic approach for the most common NPHP1 -associated ciliopathies. We demonstrated that prostaglandin E 1 rescues defective ciliogenesis and ciliary composition in NPHP1 patient urine-derived renal tubular cells and improves ciliary and kidney phenotypes in our NPH zebrafish and Nphp1 −/− mouse models. In addition, Taprenepag alleviates the severe retinopathy observed in Nphp1 −/− mice. Finally, transcriptomic analyses pointed out several pathways downstream the prostaglandin receptors as cell cycle progression, extracellular matrix, or actin cytoskeleton organization. Altogether, our findings provide an alternative for treatment of NPH.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2115960119

Reference67 articles.

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3. Nephronophthisis

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