Open AccessAgonists of prostaglandin E 2 receptors as potential first in class treatment for nephronophthisis and related ciliopathies
Author(s) -
Hugo García,
Alice Serafin,
Flora Silbermann,
Esther Porée,
Amandine Viau,
Clémentine Mahaut,
Katy Billot,
Éléonore Birgy,
Meriem Garfa-Traoré,
Stéphanie Roy,
Salomé Ceccarelli,
Ma Mehraz,
Pamela C. Rodriguez,
Bérangère Deleglise,
Laetitia Furio,
Fabienne JabotHanin,
Nicolas Cagnard,
Elaine Del Nery,
Marc Fila,
Soraya Sin-Monnot,
Corinne Antignac,
Stanislas Lyonnet,
Pauline Krug,
Rémi Salomon,
JeanPhilippe Annereau,
Alexandre Benmerah,
Marion Delous,
Luis Briseño-Roa,
Sophie Saunier
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2115960119
Subject(s) - nephronophthisis , cilium , ciliopathies , biology , ciliopathy , ciliogenesis , nocturia , microbiology and biotechnology , phenotype , endocrinology , genetics , gene , urinary system
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 E2 receptors as a potential therapeutic approach for the most commonNPHP1 -associated ciliopathies. We demonstrated that prostaglandin E1 rescues defective ciliogenesis and ciliary composition inNPHP1 patient urine-derived renal tubular cells and improves ciliary and kidney phenotypes in our NPH zebrafish andNphp1−/− mouse models. In addition, Taprenepag alleviates the severe retinopathy observed inNphp1−/− 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.