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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., 109213 (2022)
Open Access Green: Postprint online verfügbar 01/2024
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
ISSN (print) / ISBN 1521-6616
e-ISSN 1521-7035
Zeitschrift Clinical Immunology
Quellenangaben Band: , Heft: , Seiten: 109213 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed