2026-04-13T07:14:54Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1268792025-12-05T12:11:27Zcom_2072_1057col_2072_478916col_2072_478917

urn:hdl:2445/126879 Macrophage-derived Lipocalin-2 contributes to ischemic resistance mechanisms by protecting from renal injury Jung, Michaela Brüne, Bernhard, 1957- Hotter Corripio, Georgina Sola Martínez, Anna Insuficiència renal Macròfags Renal insufficiency Macrophages Renal ischemia-reperfusion injury triggers an inflammatory response associated to infiltrating macrophages which determines the further outcome of disease. Brown Norway rats are known to show endogenous resistance to ischemia-induced renal damage. By contrast, Sprague Dawley rats exhibit a higher susceptibility to ischemic injury. In order to ascertain cytoprotective mechanisms, we focused on the implication of lipocalin-2 protein in main resistance mechanisms in renal ischemia/reperfusion injury by using adoptive macrophage administration, genetically modified ex vivo either to overexpress or to knockdown lipocalin-2. In vitro experiments with bone marrow-derived macrophages both from Brown Norway rats and from Sprague Dawley rats under hypoxic conditions showed endogenous differences regarding cytokine and lipocalin-2 expression profile in the two strains. Most interestingly, we observed that macrophages of the resistant strain express significantly more lipocalin-2. In vivo studies showed that tubular epithelial cell apoptosis and renal injury significantly increased and reparative markers decreased in Brown Norway rats after injection of lipocalin-2-knockdown macrophages, while the administration of lipocalin-2-overexpressing cells significantly decreased Sprague Dawley susceptibility. These data point to a crucial role of macrophage-derived lipocalin-2 in endogenous cytoprotective mechanisms. We conclude that expression of lipocalin-2 in tissue-infiltrating macrophages is pivotal for kidney-intrinsic cytoprotective pathways during ischemia reperfusion injury. 2018-12-11T11:10:31Z 2018-12-11T11:10:31Z 2016-02-25 2018-07-25T07:52:12Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1038/srep21950 Scientific Reports, 2016, vol. 6 https://doi.org/10.1038/srep21950 cc by (c) Jung et al., 2016 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Nature Publishing Group Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))