2024-03-28T17:15:44Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1487432021-12-28T15:48:42Zcom_10261_105com_10261_1col_10261_358
Macrophage-derived Lipocalin-2 contributes to ischemic resistance mechanisms by protecting from renal injury
Jung, Michaela
Brüne, Bernhard
Hotter, Georgina
Solà, Anna M.
Instituto de Salud Carlos III
European Commission
Fritz Thyssen Foundation
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.
2017-04-24T10:13:01Z
2017-04-24T10:13:01Z
2016-02-25
2017-04-24T10:14:04Z
artículo
Scientific Reports 6: 21950 (2016)
http://hdl.handle.net/10261/148743
10.1038/srep21950
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003390
26911537
eng
Publisher's version
https://doi.org/10.1038/srep21950
Sí
https://creativecommons.org/licenses/by/4.0/
openAccess
Nature Publishing Group