PUBLICATION
Agonists of prostaglandin E2 receptors as potential first in class treatment for nephronophthisis and related ciliopathies
- Authors
- Garcia, H., Serafin, A.S., Silbermann, F., Porée, E., Viau, A., Mahaut, C., Billot, K., Birgy, É., Garfa-Traore, M., Roy, S., Ceccarelli, S., Mehraz, M., Rodriguez, P.C., Deleglise, B., Furio, L., Jabot-Hanin, F., Cagnard, N., Del Nery, E., Fila, M., Sin-Monnot, S., Antignac, C., Lyonnet, S., Krug, P., Salomon, R., Annereau, J.P., Benmerah, A., Delous, M., Briseño-Roa, L., Saunier, S.
- ID
- ZDB-PUB-220429-16
- Date
- 2022
- Source
- Proceedings of the National Academy of Sciences of the United States of America 119: e2115960119 (Journal)
- Registered Authors
- Delous, Marion, Garcia, Hugo, Lyonnet, Stanislas, Saunier, Sophie
- Keywords
- drug-screen, kidney, nephronophthisis, primary cilia, prostaglandins
- MeSH Terms
-
- Animals
- Cilia/metabolism
- Ciliopathies*/drug therapy
- Ciliopathies*/genetics
- Ciliopathies*/metabolism
- Female
- Humans
- Kidney Diseases, Cystic/congenital
- Male
- Mice
- Polycystic Kidney Diseases*/metabolism
- Prostaglandins/metabolism
- Receptors, Prostaglandin E/metabolism
- Zebrafish
- PubMed
- 35482924 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Garcia, H., Serafin, A.S., Silbermann, F., Porée, E., Viau, A., Mahaut, C., Billot, K., Birgy, É., Garfa-Traore, M., Roy, S., Ceccarelli, S., Mehraz, M., Rodriguez, P.C., Deleglise, B., Furio, L., Jabot-Hanin, F., Cagnard, N., Del Nery, E., Fila, M., Sin-Monnot, S., Antignac, C., Lyonnet, S., Krug, P., Salomon, R., Annereau, J.P., Benmerah, A., Delous, M., Briseño-Roa, L., Saunier, S. (2022) Agonists of prostaglandin E2 receptors as potential first in class treatment for nephronophthisis and related ciliopathies. Proceedings of the National Academy of Sciences of the United States of America. 119:e2115960119.
Abstract
SignificanceJuvenile 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 E2 receptors as a potential therapeutic approach for the most common NPHP1-associated ciliopathies. We demonstrated that prostaglandin E1 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping