Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis

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Fältnamn	Indikatorer	Metadata
000		10562naa a2200793 4500
001		oai:DiVA.org:uu-524644
003		SwePub
008		240313s2024 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5246442 URI
024	7	a https://doi.org/10.1038/s41420-024-01857-z2 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Medina-Dols, Ainau Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.4 aut
245	1 0	a Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis
264	1	b Springer Nature,c 2024
338		a electronic2 rdacarrier
520		a Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) <= 2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1 alpha also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ss, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, beta-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
700	1	a Canellas, Guillemu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Capo, Toniu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Sole, Montseu Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.4 aut
700	1	a Mola-Caminal, Marinau Uppsala universitet,Medicinsk epidemiologi,Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain.4 aut0 (Swepub:uu)marmo445
700	1	a Cullell, Nataliau Hosp Univ Mutua Terrassa, Neurol, Fundacio Docencia & Recerca Mutua Terrassa, Terrassa, Spain.;Inst Recerca St Pau IR ST PAU, Stroke Pharmacogen & Genet, Barcelona, Spain.4 aut
700	1	a Jaume, Marinau Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Nadal-Salas, Laurau Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Llinas, Jaumeu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Gomez, Lluisu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Tur, Silviau Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Hosp Univ Son Espases HUSE, Dept Neurol, Palma De Mallorca, Spain.4 aut
700	1	a Jimenez, Carmenu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Hosp Univ Son Espases HUSE, Dept Neurol, Palma De Mallorca, Spain.4 aut
700	1	a Diaz, Rosa M.u Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Hosp Univ Son Espases HUSE, Dept Neurol, Palma De Mallorca, Spain.4 aut
700	1	a Carrera, Catyu Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.;Inst Recerca St Pau IR ST PAU, Stroke Pharmacogen & Genet, Barcelona, Spain.4 aut
700	1	a Muino, Elenau Inst Recerca St Pau IR ST PAU, Stroke Pharmacogen & Genet, Barcelona, Spain.4 aut
700	1	a Gallego-Fabrega, Cristinau Inst Recerca St Pau IR ST PAU, Stroke Pharmacogen & Genet, Barcelona, Spain.4 aut
700	1	a Soriano-Tarraga, Carolinau Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain.4 aut
700	1	a Ruiz-Guerra, Laurau Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.4 aut
700	1	a Pol-Fuster, Josepu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Asensio, Victoru Dept Genet GEN IB, HUSE, IdISBa, Palma De Mallorca, Spain.4 aut
700	1	a Muncunill, Josepu Genom & Bioinformat Platform, IdISBa, Palma De Mallorca, Spain.4 aut
700	1	a Fleischer, Aarneu Genom & Bioinformat Platform, IdISBa, Palma De Mallorca, Spain.4 aut
700	1	a Iglesias, Amandau Hosp Univ Son Espases IdISBa Palma, Dept Resp Med, Palma De Mallorca, Spain.;Inst Salud Carlos III, CIBERES, Madrid, Spain.;CIBER Resp Dis CIBERES, Madrid, Spain.4 aut
700	1	a Giralt-Steinhauer, Evau Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain.4 aut
700	1	a Lazcano, Uxueu Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain.4 aut
700	1	a Fernandez-Perez, Isabelu Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain.4 aut
700	1	a Jimenez-Balado, Joanu Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain.4 aut
700	1	a Gabriel-Salazar, Marinau Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.4 aut
700	1	a Garcia-Gabilondo, Miguelu Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.4 aut
700	1	a Lei, Tingu Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.4 aut
700	1	a Torres-Aguila, Nuria-Pazu Inst Recerca St Pau IR ST PAU, Stroke Pharmacogen & Genet, Barcelona, Spain.4 aut
700	1	a Carcel-Marquez, Jarau Inst Recerca St Pau IR ST PAU, Stroke Pharmacogen & Genet, Barcelona, Spain.4 aut
700	1	a Llado, Jeroniau Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Olmos, Gabrielu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
700	1	a Rosell, Annau Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.4 aut
700	1	a Montaner, Joanu Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.;Univ Seville, CSIC, Inst Biomed Sevilla,IBiS, Seville, Spain.;Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain.4 aut
700	1	a Planas, Anna M.u CSIC, Inst Invest Biomed Barcelona IIBB, Dept Neurosci & Expt Therapeut, Barcelona, Spain.;Inst Invest Biomed August Pi I Sunyer IDIBAPS, Area Neurosci, Barcelona, Spain.4 aut
700	1	a Rabionet, Raquelu Univ Barcelona UB, Dept Genet Microbiol & Stat, Barcelona, Spain.;Inst Recerca St Joan de Deu, Barcelona, Spain.;Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain.4 aut
700	1	a Hernandez-Guillamon, Maru Univ Autonoma Barcelona, Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain.4 aut
700	1	a Jimenez-Conde, Jordiu Hosp del Mar Med Res Inst, Neurol, Barcelona, Spain.4 aut
700	1	a Fernandez-Cadenas, Israelu Inst Recerca St Pau IR ST PAU, Stroke Pharmacogen & Genet, Barcelona, Spain.4 aut
700	1	a Vives-Bauza, Cristofolu Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 aut
710	2	a Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.b Hosp Univ Son Espases, Hlth Res Inst Balear Isl IdISBa, Res Unit, Neurobiol Lab, Palma De Mallorca, Spain.;Univ Balear Isl UIB, Inst Univ Invest Ciencies Salut IUNICS, Dept Biol, Palma De Mallorca, Spain.4 org
773	0	t Cell Death Discoveryd : Springer Natureg 10q 10x 2058-7716
856	4	u https://doi.org/10.1038/s41420-024-01857-zy Fulltext
856	4	u https://uu.diva-portal.org/smash/get/diva2:1844137/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524644
856	4 8	u https://doi.org/10.1038/s41420-024-01857-z

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Av författaren/redakt...: Medina-Dols, Ain ...; Canellas, Guille ...; Capo, Toni; Sole, Montse; Mola-Caminal, Ma ...; Cullell, Natalia; visa fler...; Jaume, Marina; Nadal-Salas, Lau ...; Llinas, Jaume; Gomez, Lluis; Tur, Silvia; Jimenez, Carmen; Diaz, Rosa M.; Carrera, Caty; Muino, Elena; Gallego-Fabrega, ...; Soriano-Tarraga, ...; Ruiz-Guerra, Lau ...; Pol-Fuster, Jose ...; Asensio, Victor; Muncunill, Josep; Fleischer, Aarne; Iglesias, Amanda; Giralt-Steinhaue ...; Lazcano, Uxue; Fernandez-Perez, ...; Jimenez-Balado, ...; Gabriel-Salazar, ...; Garcia-Gabilondo ...; Lei, Ting; Torres-Aguila, N ...; Carcel-Marquez, ...; Llado, Jeronia; Olmos, Gabriel; Rosell, Anna; Montaner, Joan; Planas, Anna M.; Rabionet, Raquel; Hernandez-Guilla ...; Jimenez-Conde, J ...; Fernandez-Cadena ...; Vives-Bauza, Cri ...; visa färre...

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