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LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1

Title
LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1
Authors
Yoo J.-Y.Cha D.R.Kim B.An E.J.Lee S.R.Cha J.J.Kang Y.S.Ghee J.Y.Han J.Y.Bae Y.S.
Ewha Authors
배윤수
SCOPUS Author ID
배윤수scopus
Issue Date
2020
Journal Title
Cell Reports
ISSN
2211-1247JCR Link
Citation
Cell Reports vol. 33, no. 3
Keywords
AKIcytokineH2O2, LPSinflammationNox4sepsisSH3YL1TLR4tubular damage
Publisher
Elsevier B.V.
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Cytosolic proteins are required for regulation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) isozymes. Here we show that Src homology 3 (SH3) domain-containing YSC84-like 1 (SH3YL1), as a Nox4 cytosolic regulator, mediates lipopolysaccharide (LPS)-induced H2O2 generation, leading to acute kidney injury. The SH3YL1, Ysc84p/Lsb4p, Lsb3p, and plant FYVE proteins (SYLF) region and SH3 domain of SH3YL1 contribute to formation of a complex with Nox4-p22phox. Interaction of p22phox with SH3YL1 is triggered by LPS, and the complex induces H2O2 generation and pro-inflammatory cytokine expression in mouse tubular epithelial cells. After LPS injection, SH3YL1 knockout mice show lower levels of acute kidney injury biomarkers, decreased secretion of pro-inflammatory cytokines, decreased infiltration of macrophages, and reduced tubular damage compared with wild-type (WT) mice. The results strongly suggest that SH3YL1 is involved in renal failure in LPS-induced acute kidney injury (AKI) mice. We demonstrate that formation of a ternary complex of p22phox-SH3YL1-Nox4, leading to H2O2 generation, induces severe renal failure in the LPS-induced AKI model. Yoo et al. demonstrate that SH3YL1 serves as a cytosolic regulator of Nox4 to mediate LPS-dependent H2O2 generation. The Nox4-SH3YL1 axis stimulates expression of pro-inflammatory cytokines and then triggers apoptosis of tubular cells, leading to AKI. SH3YL1 plays an important role in diseases associated with H2O2 produced by Nox4. © 2020 The Authors
DOI
10.1016/j.celrep.2020.108245
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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