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Alli, A.A.* ; Desai, D.* ; Elshika, A.* ; Conrad, M. ; Proneth, B. ; Clapp, W.* ; Atkinson, C.* ; Segal, M.G.* ; Searcy, L.A.* ; Denslow, N.D.* ; Bolisetty, S.* ; Mehrad, B.* ; Morel, L.* ; Scindia, Y.*

Kidney tubular epithelial cell ferroptosis links glomerular injury to tubulointerstitial pathology in lupus nephritis.

Clin. Immunol. 248:109213 (2022)
Postprint DOI PMC
Open Access Green
Ferroptosis is a druggable, iron-dependent form of cell death that is characterized by lipid peroxidation but has received little attention in lupus nephritis. Kidneys of lupus nephritis patients and mice showed increased lipid peroxidation mainly in the tubular segments and an increase in Acyl-CoA synthetase long-chain family member 4, a pro-ferroptosis enzyme. Nephritic mice had an attenuated expression of SLC7A11, a cystine importer, an impaired glutathione synthesis pathway, and low expression of glutathione peroxidase 4, a ferroptosis inhibitor. Lipidomics of nephritic kidneys confirmed ferroptosis. Using nephrotoxic serum, we induced immune complex glomerulonephritis in congenic mice and demonstrate that impaired iron sequestration within the proximal tubules exacerbates ferroptosis. Lupus nephritis patient serum rendered human proximal tubular cells susceptibility to ferroptosis which was inhibited by Liproxstatin-2, a novel ferroptosis inhibitor. Collectively, our findings identify intra-renal ferroptosis as a pathological feature and contributor to tubular injury in human and murine lupus nephritis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acsl4 ; Ferroptosis ; Gpx4 ; Iron ; Liproxstatin ; Lupus Nephritis ; Sle; Anti-dsdna Antibodies; Iron Homeostasis; Arachidonic-acid; Renal-disease; T-cells; Death; Pathogenesis; Chain; Mice; Erythematosus
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 1521-6616
e-ISSN 1521-7035
Zeitschrift Clinical Immunology
Quellenangaben Band: 248, Heft: , Seiten: , Artikelnummer: 109213 Supplement: ,
Verlag Elsevier
Verlagsort 525 B St, Ste 1900, San Diego, Ca 92101-4495 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506900-001
Förderungen NIH
Vifor Pharma
DOI 10.1016/j.clim.2022.109213
WOS ID 000939583700001
Scopus ID 85148011276
PubMed ID 36566913
Erfassungsdatum 2023-01-16
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