Liver osteopontin is required to prevent the progression of age-related nonalcoholic fatty liver disease
dc.contributor.author | Gómez Santos, Beatriz | |
dc.contributor.author | Saenz de Urturi Indart, Diego | |
dc.contributor.author | Nuñez García, Maitane | |
dc.contributor.author | González Romero, Francisco | |
dc.contributor.author | Buqué García, Xabier | |
dc.contributor.author | Aurrekoetxea Galindo, Igor | |
dc.contributor.author | Gutiérrez de Juan, Virginia | |
dc.contributor.author | González Rellán, María Jesús | |
dc.contributor.author | García Monzón, Carmelo | |
dc.contributor.author | González Rodríguez, Águeda | |
dc.contributor.author | Mosteiro González, Lorena | |
dc.contributor.author | Errazti Olartecoechea, Gaizka | |
dc.contributor.author | Mifsut Porcel, Patricia | |
dc.contributor.author | Gaztambide Sáenz, María Sonia | |
dc.contributor.author | Castaño González, Luis Antonio | |
dc.contributor.author | Martín Plágaro, César Augusto | |
dc.contributor.author | Nogueiras Pozo, Rubén | |
dc.contributor.author | Martínez Chantar, María Luz | |
dc.contributor.author | Syn, Wing-Kin | |
dc.contributor.author | Aspichueta Celaá, Patricia | |
dc.date.accessioned | 2020-09-30T18:29:36Z | |
dc.date.available | 2020-09-30T18:29:36Z | |
dc.date.issued | 2020-07-07 | |
dc.identifier.citation | Aging Cell 19(8) : (2020) // e13183 | es_ES |
dc.identifier.issn | 1474-9718 | |
dc.identifier.uri | http://hdl.handle.net/10810/46301 | |
dc.description.abstract | [EN] Osteopontin (OPN), a senescence-associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age-dependent hepatosteatosis. Thus, we investigated the role of OPN in the age-related hepatosteatosis. For this, human serum samples, animal models of aging, and cell lines in which senescence was induced were used. Metabolic fluxes, lipid, and protein concentration were determined. Among individuals with a normal liver, we observed a positive correlation between serum OPN levels and increasing age. This correlation with age, however, was absent in patients with NAFLD. In wild-type (WT) mice, serum and liver OPN were increased at 10 months old (m) along with liver p53 levels and remained elevated at 20m. Markers of liver senescence increased in association with synthesis and concentration of triglycerides (TG) in 10m OPN-deficient (KO) hepatocytes when compared to WT hepatocytes. These changes in senescence and lipid metabolism in 10m OPN-KO mice liver were associated with the decrease of 78 kDa glucose-regulated protein (GRP78), induction of ER stress, and the increase in fatty acid synthase and CD36 levels. OPN deficiency in senescent cells also diminished GRP78, the accumulation of intracellular TG, and the increase in CD36 levels. In 20m mice, OPN loss led to increased liver fibrosis. Finally, we showed that OPN expression in vitro and in vivo was regulated by p53. In conclusion, OPN deficiency leads to earlier cellular senescence, ER stress, and TG accumulation during aging. The p53-OPN axis is required to inhibit the onset of agerelated hepatosteatosis. | es_ES |
dc.description.sponsorship | This work was supported by Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT971‐16 to P.A.), MINECO‐FEDER (SAF2017‐87301‐R to M.L.M‐Ch) MCIU/AEI/FEDER, UE (RTI2018‐095134‐B‐100 to P.A. and RTI2018‐099413‐B‐I00 to RN, Asociación Española contra el Cáncer, Canceres raros (M.L.M‐Ch), La Caixa Foundation (to M.L.M‐Ch), Ayudas Fundación BBVA a equipos de Investigación Científica 2018 (to M.L.M‐Ch), Xunta de Galicia (RN: 2015‐CP080 and 2016‐ PG057), Fundación BBVA (RN), and European Foundation for the Study of Diabetes (RN). ISCIII‐FEDER PI17/00535 (to C.G‐M.), ISCIII‐FEDER CP14/00181 and PI16/00823 (to A.G‐ R.), and Francisco Cobos Foundation (to A.G‐R.). CiC bioGUNE thanks MINECO for the Severo Ochoa Excellence Accreditation (SEV‐2016‐ 0644) | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-87301-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RTI2018‐095134‐B‐100 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIU/RTI2018‐099413‐B‐I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | aging | es_ES |
dc.subject | lipid metabolism | es_ES |
dc.subject | nonalcoholic fatty liver disease | es_ES |
dc.subject | osteopontin | es_ES |
dc.subject | p53 | es_ES |
dc.subject | senescence | es_ES |
dc.title | Liver osteopontin is required to prevent the progression of age-related nonalcoholic fatty liver disease | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13183 | es_ES |
dc.identifier.doi | 10.1111/acel.13183 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoes | Especialidades médico-quirúrgicas | es_ES |
dc.departamentoes | Fisiología | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
dc.departamentoeu | Fisiologia | es_ES |
dc.departamentoeu | Medikuntza eta kirurgia espezialitateak | es_ES |
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Except where otherwise noted, this item's license is described as © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.