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Seleznik, G.M.* ; Seeger, H.* ; Bauer, J. ; Fu, K.* ; Czerkowicz, J.* ; Papandile, A.* ; Poreci, U.* ; Rabah, D.* ; Ranger, A.* ; Cohen, C.D.* ; Lindenmeyer, M.* ; Chen, J.* ; Edenhofer, I.* ; Anders, H.J.* ; Lech, M.* ; Wüthrich, R.P.* ; Ruddle, N.H.* ; Moeller, M.J.* ; Kozakowski, N.* ; Regele, H.* ; Browning, J.L.* ; Heikenwälder, M. ; Segerer, S.*

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation.

Kidney Int. 89, 113–126 (2015)
Verlagsversion Anhang Anhang DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0085-2538
e-ISSN 1523-1755
Zeitschrift Kidney International
Quellenangaben Band: 89, Heft: 1, Seiten: 113–126 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-551600-001
PubMed ID 26398497
DOI 10.1038/ki.2015.280
Erfassungsdatum 2015-10-13
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