Transcriptomics and translatomics identify a robust inflammatory gene signature in brain endothelial cells after ischemic stroke
Arbaizar-Rovirosa, María (Universitat de Barcelona)
Gallizioli, Mattia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Lozano, Juan José (Bioinformatics Platform. Centro de Investigación Biomédica en Red Enfermedades Hepáticas Y Digestivas)
Sidorova, Júlia (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Pedragosa, Jordi (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Figuerola, Sara (Universitat de Barcelona)
Chaparro-Cabanillas, Nerea (Universitat de Barcelona)
Boya, P. (Department of Neuroscience and Movement Science. University of Friburg)
Graupera, Mariona (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Claret, Marc (Hospital Clínic i Provincial de Barcelona)
Planas, Anna Maria (Universitat de Barcelona)

Fecha:	2023
Resumen:	Vascular endothelial function is challenged during cerebral ischemia and reperfusion. The endothelial responses are involved in inflammatory leukocyte attraction, adhesion and infiltration, blood-brain barrier leakage, and angiogenesis. This study investigated gene expression changes in brain endothelial cells after acute ischemic stroke using transcriptomics and translatomics. We isolated brain endothelial mRNA by: (i) translating ribosome affinity purification, enabling immunoprecipitation of brain endothelial ribosome-attached mRNA for translatome sequencing and (ii) isolating CD31 endothelial cells by fluorescence-activating cell sorting for classical transcriptomic analysis. Both techniques revealed similar pathways regulated by ischemia but they showed specific differences in some transcripts derived from non-endothelial cells. We defined a gene set characterizing the endothelial response to acute stroke (24h) by selecting the differentially expressed genes common to both techniques, thus corresponding with the translatome and minimizing non-endothelial mRNA contamination. Enriched pathways were related to inflammation and immunoregulation, angiogenesis, extracellular matrix, oxidative stress, and lipid trafficking and storage. We validated, by flow cytometry and immunofluorescence, the protein expression of several genes encoding cell surface proteins. The inflammatory response was associated with the endothelial upregulation of genes related to lipid storage functions and we identified lipid droplet biogenesis in the endothelial cells after ischemia. The study reports a robust translatomic signature of brain endothelial cells after acute stroke and identifies enrichment in novel pathways involved in membrane signaling and lipid storage. Altogether these results highlight the endothelial contribution to the inflammatory response, and identify novel molecules that could be targets to improve vascular function after ischemic stroke.
Ayudas:	Instituto de Salud Carlos III PI21/00966 Agencia Estatal de Investigación PID2020-113202RB-I00
Nota:	Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Schemic stroke ; Microvasculature ; RiboTag ; Fluorescence-activated cell sorting ; Inflammation ; Lipids
Publicado en:	Journal of neuroinflammation, Vol. 20 Núm. 1 (december 2023) , p. 207, ISSN 1742-2094

DOI: 10.1186/s12974-023-02888-6
PMID: 37691115

19 p, 13.7 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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