LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1
Summary: 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 generat...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2020-10-01
|
Series: | Cell Reports |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720312341 |
id |
doaj-c4db8bbe17f14753bfe684222bc94359 |
---|---|
record_format |
Article |
spelling |
doaj-c4db8bbe17f14753bfe684222bc943592020-11-25T03:56:36ZengElsevierCell Reports2211-12472020-10-01333108245LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1Jung-Yeon Yoo0Dae Ryong Cha1Borim Kim2Eun Jung An3Sae Rom Lee4Jin Joo Cha5Young Sun Kang6Jung Yeon Ghee7Jee Young Han8Yun Soo Bae9Department of Life Sciences, Ewha Womans University, Seoul 120-750, KoreaDepartment of Internal Medicine, Division of Nephrology, Korea University Ansan Hospital, 516 Kojan-Dong, Ansan City, Kyungki-Do 425-020, KoreaDepartment of Life Sciences, Ewha Womans University, Seoul 120-750, KoreaDepartment of Life Sciences, Ewha Womans University, Seoul 120-750, KoreaDepartment of Life Sciences, Ewha Womans University, Seoul 120-750, KoreaDepartment of Internal Medicine, Division of Nephrology, Korea University Ansan Hospital, 516 Kojan-Dong, Ansan City, Kyungki-Do 425-020, KoreaDepartment of Internal Medicine, Division of Nephrology, Korea University Ansan Hospital, 516 Kojan-Dong, Ansan City, Kyungki-Do 425-020, KoreaDepartment of Internal Medicine, Division of Nephrology, Korea University Ansan Hospital, 516 Kojan-Dong, Ansan City, Kyungki-Do 425-020, KoreaDepartment of Pathology, Inha University, Incheon, KoreaDepartment of Life Sciences, Ewha Womans University, Seoul 120-750, Korea; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720312341Nox4SH3YL1H2O2, LPSsepsisAKITLR4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jung-Yeon Yoo Dae Ryong Cha Borim Kim Eun Jung An Sae Rom Lee Jin Joo Cha Young Sun Kang Jung Yeon Ghee Jee Young Han Yun Soo Bae |
spellingShingle |
Jung-Yeon Yoo Dae Ryong Cha Borim Kim Eun Jung An Sae Rom Lee Jin Joo Cha Young Sun Kang Jung Yeon Ghee Jee Young Han Yun Soo Bae LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1 Cell Reports Nox4 SH3YL1 H2O2, LPS sepsis AKI TLR4 |
author_facet |
Jung-Yeon Yoo Dae Ryong Cha Borim Kim Eun Jung An Sae Rom Lee Jin Joo Cha Young Sun Kang Jung Yeon Ghee Jee Young Han Yun Soo Bae |
author_sort |
Jung-Yeon Yoo |
title |
LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1 |
title_short |
LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1 |
title_full |
LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1 |
title_fullStr |
LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1 |
title_full_unstemmed |
LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1 |
title_sort |
lps-induced acute kidney injury is mediated by nox4-sh3yl1 |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2020-10-01 |
description |
Summary: 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. |
topic |
Nox4 SH3YL1 H2O2, LPS sepsis AKI TLR4 |
url |
http://www.sciencedirect.com/science/article/pii/S2211124720312341 |
work_keys_str_mv |
AT jungyeonyoo lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT daeryongcha lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT borimkim lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT eunjungan lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT saeromlee lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT jinjoocha lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT youngsunkang lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT jungyeonghee lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT jeeyounghan lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 AT yunsoobae lpsinducedacutekidneyinjuryismediatedbynox4sh3yl1 |
_version_ |
1724464021612003328 |