Browsing by Author "González, Alfonso"
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- ItemFact or Fiction, It Is Time for a Verdict on Vasculogenic Mimicry?(2019) Valdivia Román, Andrés Felipe; Mingo Orsini, Gabriel Antonio; Aldana, Varina; Pinto, Mauricio P.; Ramírez, Marco; Retamal, Claudio; González, Alfonso; Nualart, Francisco; Corválan, Alejandro H.; Owen, Gareth Ivor
- ItemGalectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis(2017) Pardo, Evelyn; Cárcamo, Claudia; Uribe-San Martín, Reinaldo; Ciampi, Ethel; Segovia-Miranda, Fabián; Curkovic-Peña, Cristobal; Montecino, Fabián; Holmes, Christopher; Tichauer, Juan Enrique; Acuña, Eric; Osorio-Barrios, Francisco; Castro, Marjorie; Cortes, Priscilla; Oyanadel, Claudia; Valenzuela, David M.; Pacheco, Rodrigo; Naves, Rodrigo; Soza, Andrea; González, AlfonsoGalectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.
- ItemGalectin-8 induces partial epithelial–mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin–Darby canine kidney cells(2018) Oyanadel, Claudia; Holmes Videla, Christopher Edward; Pardo Huguet, Evelyn Cristina; Retamal Villarroel, Claudio Enrique; Shaughnessy, Ronan Patrick; Smith, Patricio C.; Cortés Martínez, Priscilla Rocío; Bravo Zehnder, Marcela; Metz Baer, Claudia Andrea; Feuerhake, Teo; Romero, Diego; Roa Strauch, Juan Carlos Enrique; Montecinos, Viviana; Soza Gajardo, Andrea; González, Alfonso
- ItemInhibidores de fosfohidrolasa de ácido fosfatídico (PAP), incluyendo D-propranolol y análogos, solos o en combinación con desipramina, para bloquear cánceres dependientes del EGFR, sus variantes oncogénicas y otros miembros de su familia ErbB/HERGonzález, Alfonso; Soza Gajardo, Andrea; Metz Baer, Claudia Andrea
- ItemKDEL receptor regulates secretion by lysosome relocation- and autophagy-dependent modulation of lipid-droplet turnover(2019) Tapia, Diego; Zamora, Constanza; Espinoza, Javier; Rizzo, Riccardo; González Cárdenas, Alexis; Fuentes Peña, Danitza Natalia; Hernández, Sergio; Cavieres, Viviana A.; Guzmán, Fanny; Arriagada, Gloria; Yuseff Sepúlveda, María Isabel; Mardones, Gonzalo A.; Burgos , Patricia V.; Luini, Alberto; González, Alfonso; Cancino, Jorge; Jiménez, Tomás; Soza Gajardo, Andrea
- ItemResistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome(2017) Macanas Pirard, Patricia; Broekhuizen, Richard; González, Alfonso; Oyanadel, Claudia; Ernst Diaz, Daniel Matias; García Cañete, Patricia; Montecinos Acuña, Viviana; Court G., Felipe; Ocqueteau Tachini, Mauricio; Ramírez Villanueva, Pablo Antonio; Nervi, Bruno