Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/283035
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function |
Autor: | Martín-Vázquez, Eugenia CSIC; Cobo-Vuilleumier, Nadia CSIC ORCID; Araujo Legido, Raquel CSIC ORCID; Marín-Cañas, Sandra; Nola, Emanuele; Dorronsoro, Akaitz CSIC ORCID; López-Bermudo, Lucía CSIC ORCID; Crespo Barreda, Alejandra CSIC; Romero-Zerbo, Silvana Y.; García-Fernández, María; Martín-Montalvo, Alejandro CSIC ORCID; Rojas, Anabel CSIC ORCID; Comaills, Valentine CSIC ORCID; Bermúdez-Silva, Francisco Javier; Gannon, Marueen; Martín, Franz CSIC ORCID; Eizirik, Decio L.; Lorenzo, Petra Isabel CSIC ORCID; Gauthier, Benoit R. CSIC ORCID | Fecha de publicación: | 20-may-2022 | Editor: | Cell Press | Citación: | iScience 25(5): 104345 (2022) | Resumen: | LRH-1/NR5A2 is implicated in islet morphogenesis postnatally, and its activation using the agonist BL001 protects islets against apoptosis, reverting hyperglycemia in mouse models of Type 1 Diabetes Mellitus. Islet transcriptome profiling revealed that the expression of PTGS2/COX2 is increased by BL001. Herein, we sought to define the role of LRH-1 in postnatal islet morphogenesis and chart the BL001 mode of action conferring beta cell protection. LRH-1 ablation within developing beta cells impeded beta cell proliferation, correlating with mouse growth retardation, weight loss, and hypoglycemia leading to lethality. LRH-1 deletion in adult beta cells abolished the BL001 antidiabetic action, correlating with beta cell destruction and blunted Ptgs2 induction. Islet PTGS2 inactivation led to reduced PGE levels and loss of BL001 protection against cytokines as evidenced by increased cytochrome c release and cleaved-PARP. The PTGER1 antagonist—ONO-8130—negated BL001-mediated islet survival. Our results define the LRH-1/PTGS2/PGE/PTGER1 signaling axis as a key pathway mediating BL001 survival properties. | Versión del editor: | http://dx.doi.org/10.1016/j.isci.2022.104345 | URI: | http://hdl.handle.net/10261/283035 | DOI: | 10.1016/j.isci.2022.104345 | Identificadores: | e-issn: 2589-0042 |
Aparece en las colecciones: | (CABIMER) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
1-s2.0-S2589004222006162-main.pdf | 5,2 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
9
checked on 24-abr-2024
WEB OF SCIENCETM
Citations
4
checked on 25-feb-2024
Page view(s)
56
checked on 24-abr-2024
Download(s)
57
checked on 24-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Este item está licenciado bajo una Licencia Creative Commons