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@ARTICLE{Lux:141759,
author = {M. Lux and A. Blaut and N. Eltrich and A. Bideak and M. B.
Müller and J. M. Hoppe and H.-J. Gröne$^*$ and M. Locati
and V. Vielhauer},
title = {{T}he atypical chemokine receptor 2 limits progressive
fibrosis after acute ischemic kidney injury.},
journal = {The American journal of pathology},
volume = {189},
number = {2},
issn = {0002-9440},
address = {New York [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2018-02028},
pages = {231-247},
year = {2019},
abstract = {Following renal ischemia-reperfusion injury (IRI)
resolution of inflammation allows tubular regeneration,
whereas ongoing inflammatory injury mediated by infiltrating
leukocytes leads to nephron loss and renal fibrosis, typical
hallmarks of chronic kidney disease. The atypical chemokine
receptor 2 (ACKR2) is a chemokine decoy receptor, that binds
and scavenges inflammatory CC-chemokines and reduces local
leukocyte accumulation. We hypothesized that ACKR2 limits
leukocyte infiltration, inflammation, and fibrotic tissue
remodeling after renal IRI, thus preventing progression to
chronic kidney disease. Compared to wild-type, Ackr2
deficiency increased CC chemokine ligand 2 levels in tumor
necrosis factor-stimulated tubulointerstitial tissue in
vitro. In Ackr2-deficient mice with early IRI one or five
days after transient renal pedicle clamping tubular injury
was similar to wild-type, although accumulation of
mononuclear phagocytes increased in postischemic Ackr2-/-
kidneys. Regarding long-term outcomes, Ackr2-/- kidneys
displayed more tubular injury five weeks after IRI, which
was associated with persistently increased renal infiltrates
of mononuclear phagocytes, T cells, Ly6Chigh inflammatory
macrophages, and inflammation. Moreover, Ackr2 deficiency
resulted in substantially aggravated renal fibrosis in
Ackr2-/- kidneys five weeks after IRI, as revealed by
increased expression of matrix molecules, renal accumulation
of αSMA+ myofibroblasts, and bone marrow-derived
fibrocytes. ACKR2 plays an important role in limiting
persistent inflammation, tubular loss, and renal fibrosis
after ischemic acute kidney injury, and thus can prevent
progression to chronic renal disease.},
cin = {G130},
ddc = {610},
cid = {I:(DE-He78)G130-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30448408},
doi = {10.1016/j.ajpath.2018.09.016},
url = {https://inrepo02.dkfz.de/record/141759},
}