dc.contributor.author |
Jung, Michaela |
dc.contributor.author |
Brüne, Bernhard |
dc.contributor.author |
Hotter Corripio, Georgina |
dc.contributor.author |
Sola Martínez, Anna |
dc.date |
2018-12-11T11:10:31Z |
dc.date |
2018-12-11T11:10:31Z |
dc.date |
2016-02-25 |
dc.date |
2018-07-25T07:52:12Z |
dc.identifier.uri |
http://hdl.handle.net/2445/126879 |
dc.format |
13 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
Nature Publishing Group |
dc.relation |
Reproducció del document publicat a: https://doi.org/10.1038/srep21950 |
dc.relation |
Scientific Reports, 2016, vol. 6 |
dc.relation |
https://doi.org/10.1038/srep21950 |
dc.rights |
cc by (c) Jung et al., 2016 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.rights |
http://creativecommons.org/licenses/by/3.0/es/ |
dc.subject |
Insuficiència renal |
dc.subject |
Macròfags |
dc.subject |
Renal insufficiency |
dc.subject |
Macrophages |
dc.title |
Macrophage-derived Lipocalin-2 contributes to ischemic resistance mechanisms by protecting from renal injury |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/publishedVersion |
dc.description.abstract |
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. |