Agonists of prostaglandin E 2 receptors as potential first in class treatment for nephronophthisis and related ciliopathies - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2022

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

Clémentine Mahaut
  • Fonction : Auteur
Éléonore Birgy
  • Fonction : Auteur
Meriem Garfa-Traore
  • Fonction : Auteur
Pamela Rodriguez
  • Fonction : Auteur
Bérangère Deleglise
Laetitia Furio
  • Fonction : Auteur
Fabienne Jabot-Hanin
Nicolas Cagnard
  • Fonction : Auteur
Elaine del Nery
  • Fonction : Auteur
Marc Fila
  • Fonction : Auteur
Soraya Sin-Monnot
Stanislas Lyonnet
  • Fonction : Auteur
Pauline Krug
  • Fonction : Auteur
Rémi Salomon
  • Fonction : Auteur
Jean-Philippe Annereau
Luis Briseño-Roa

Résumé

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.

Dates et versions

hal-03930843 , version 1 (09-01-2023)

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Citer

Hugo Garcia, Alice Serafin, Flora Silbermann, Esther Porée, Amandine Viau, et al.. Agonists of prostaglandin E 2 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, 2022, 119 (18), ⟨10.1073/pnas.2115960119⟩. ⟨hal-03930843⟩

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