Hemojuvelin modulates iron stress during acute kidney injury: Improved by furin inhibitor

Guang Huar Young; Tao Min Huang; Che Hsiung Wu; Chun Fu Lai; Chun Cheng Hou; Kang Yung Peng; Chan Jung Liang; Shuei Liong Lin; Shih Chung Chang; Pi Ru Tsai; Kwan Dun Wu; Vin Cent Wu; Wen Je Ko

doi:10.1089/ars.2013.5366

Hemojuvelin modulates iron stress during acute kidney injury: Improved by furin inhibitor

Guang Huar Young, Tao Min Huang, Che Hsiung Wu, Chun Fu Lai, Chun Cheng Hou, Kang Yung Peng, Chan Jung Liang, Shuei Liong Lin, Shih Chung Chang, Pi Ru Tsai, Kwan Dun Wu, Vin Cent Wu, Wen Je Ko^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

22 Scopus citations

Abstract

Aims: Free iron plays an important role in the pathogenesis of acute kidney injury (AKI) via the formation of hydroxyl radicals. Systemic iron homeostasis is controlled by the hemojuvelin-hepcidin-ferroportin axis in the liver, but less is known about this role in AKI. Results: By proteomics, we identified a 42 kDa soluble hemojuvelin (sHJV), processed by furin protease from membrane-bound hemojuvelin (mHJV), in the urine during AKI after cardiac surgery. Biopsies from human and mouse specimens with AKI confirm that HJV is extensively increased in renal tubules. Iron overload enhanced the expression of hemojuvelin-hepcidin signaling pathway. The furin inhibitor (FI) decreases furin-mediated proteolytic cleavage of mHJV into sHJV and augments the mHJV/sHJV ratio after iron overload with hypoxia condition. The FI could reduce renal tubule apoptosis, stabilize hypoxic induced factor-1, prevent the accumulation of iron in the kidney, and further ameliorate ischemic-reperfusion injury. mHJV is associated with decreasing total kidney iron, secreting hepcidin, and promoting the degradation of ferroportin at AKI, whereas sHJV does the opposite. Innovation: This study suggests the ratio of mHJV/sHJV affects the iron deposition during acute kidney injury and sHJV could be an early biomarker of AKI. Conclusion: Our findings link endogenous HJV inextricably with renal iron homeostasis for the first time, add new significance to early predict AKI, and identify novel therapeutic targets to reduce the severity of AKI using the FI. Antioxid. Redox Signal. 20, 1181-1194.

Original language	English
Pages (from-to)	1181-1194
Number of pages	14
Journal	Antioxidants and Redox Signaling
Volume	20
Issue number	8
DOIs	https://doi.org/10.1089/ars.2013.5366
State	Published - 10 03 2014
Externally published	Yes

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@article{9f67a4068b214186a0d8eb2b0ace2f53,

title = "Hemojuvelin modulates iron stress during acute kidney injury: Improved by furin inhibitor",

abstract = "Aims: Free iron plays an important role in the pathogenesis of acute kidney injury (AKI) via the formation of hydroxyl radicals. Systemic iron homeostasis is controlled by the hemojuvelin-hepcidin-ferroportin axis in the liver, but less is known about this role in AKI. Results: By proteomics, we identified a 42 kDa soluble hemojuvelin (sHJV), processed by furin protease from membrane-bound hemojuvelin (mHJV), in the urine during AKI after cardiac surgery. Biopsies from human and mouse specimens with AKI confirm that HJV is extensively increased in renal tubules. Iron overload enhanced the expression of hemojuvelin-hepcidin signaling pathway. The furin inhibitor (FI) decreases furin-mediated proteolytic cleavage of mHJV into sHJV and augments the mHJV/sHJV ratio after iron overload with hypoxia condition. The FI could reduce renal tubule apoptosis, stabilize hypoxic induced factor-1, prevent the accumulation of iron in the kidney, and further ameliorate ischemic-reperfusion injury. mHJV is associated with decreasing total kidney iron, secreting hepcidin, and promoting the degradation of ferroportin at AKI, whereas sHJV does the opposite. Innovation: This study suggests the ratio of mHJV/sHJV affects the iron deposition during acute kidney injury and sHJV could be an early biomarker of AKI. Conclusion: Our findings link endogenous HJV inextricably with renal iron homeostasis for the first time, add new significance to early predict AKI, and identify novel therapeutic targets to reduce the severity of AKI using the FI. Antioxid. Redox Signal. 20, 1181-1194.",

author = "Young, {Guang Huar} and Huang, {Tao Min} and Wu, {Che Hsiung} and Lai, {Chun Fu} and Hou, {Chun Cheng} and Peng, {Kang Yung} and Liang, {Chan Jung} and Lin, {Shuei Liong} and Chang, {Shih Chung} and Tsai, {Pi Ru} and Wu, {Kwan Dun} and Wu, {Vin Cent} and Ko, {Wen Je}",

year = "2014",

month = mar,

day = "10",

doi = "10.1089/ars.2013.5366",

language = "英语",

volume = "20",

pages = "1181--1194",

journal = "Antioxidants and Redox Signaling",

issn = "1523-0864",

publisher = "Mary Ann Liebert Inc.",

number = "8",

}

TY - JOUR

T1 - Hemojuvelin modulates iron stress during acute kidney injury

T2 - Improved by furin inhibitor

AU - Young, Guang Huar

AU - Huang, Tao Min

AU - Wu, Che Hsiung

AU - Lai, Chun Fu

AU - Hou, Chun Cheng

AU - Peng, Kang Yung

AU - Liang, Chan Jung

AU - Lin, Shuei Liong

AU - Chang, Shih Chung

AU - Tsai, Pi Ru

AU - Wu, Kwan Dun

AU - Wu, Vin Cent

AU - Ko, Wen Je

PY - 2014/3/10

Y1 - 2014/3/10

N2 - Aims: Free iron plays an important role in the pathogenesis of acute kidney injury (AKI) via the formation of hydroxyl radicals. Systemic iron homeostasis is controlled by the hemojuvelin-hepcidin-ferroportin axis in the liver, but less is known about this role in AKI. Results: By proteomics, we identified a 42 kDa soluble hemojuvelin (sHJV), processed by furin protease from membrane-bound hemojuvelin (mHJV), in the urine during AKI after cardiac surgery. Biopsies from human and mouse specimens with AKI confirm that HJV is extensively increased in renal tubules. Iron overload enhanced the expression of hemojuvelin-hepcidin signaling pathway. The furin inhibitor (FI) decreases furin-mediated proteolytic cleavage of mHJV into sHJV and augments the mHJV/sHJV ratio after iron overload with hypoxia condition. The FI could reduce renal tubule apoptosis, stabilize hypoxic induced factor-1, prevent the accumulation of iron in the kidney, and further ameliorate ischemic-reperfusion injury. mHJV is associated with decreasing total kidney iron, secreting hepcidin, and promoting the degradation of ferroportin at AKI, whereas sHJV does the opposite. Innovation: This study suggests the ratio of mHJV/sHJV affects the iron deposition during acute kidney injury and sHJV could be an early biomarker of AKI. Conclusion: Our findings link endogenous HJV inextricably with renal iron homeostasis for the first time, add new significance to early predict AKI, and identify novel therapeutic targets to reduce the severity of AKI using the FI. Antioxid. Redox Signal. 20, 1181-1194.

AB - Aims: Free iron plays an important role in the pathogenesis of acute kidney injury (AKI) via the formation of hydroxyl radicals. Systemic iron homeostasis is controlled by the hemojuvelin-hepcidin-ferroportin axis in the liver, but less is known about this role in AKI. Results: By proteomics, we identified a 42 kDa soluble hemojuvelin (sHJV), processed by furin protease from membrane-bound hemojuvelin (mHJV), in the urine during AKI after cardiac surgery. Biopsies from human and mouse specimens with AKI confirm that HJV is extensively increased in renal tubules. Iron overload enhanced the expression of hemojuvelin-hepcidin signaling pathway. The furin inhibitor (FI) decreases furin-mediated proteolytic cleavage of mHJV into sHJV and augments the mHJV/sHJV ratio after iron overload with hypoxia condition. The FI could reduce renal tubule apoptosis, stabilize hypoxic induced factor-1, prevent the accumulation of iron in the kidney, and further ameliorate ischemic-reperfusion injury. mHJV is associated with decreasing total kidney iron, secreting hepcidin, and promoting the degradation of ferroportin at AKI, whereas sHJV does the opposite. Innovation: This study suggests the ratio of mHJV/sHJV affects the iron deposition during acute kidney injury and sHJV could be an early biomarker of AKI. Conclusion: Our findings link endogenous HJV inextricably with renal iron homeostasis for the first time, add new significance to early predict AKI, and identify novel therapeutic targets to reduce the severity of AKI using the FI. Antioxid. Redox Signal. 20, 1181-1194.

UR - http://www.scopus.com/inward/record.url?scp=84894448679&partnerID=8YFLogxK

U2 - 10.1089/ars.2013.5366

DO - 10.1089/ars.2013.5366

M3 - 文献综述

C2 - 23901875

AN - SCOPUS:84894448679

SN - 1523-0864

VL - 20

SP - 1181

EP - 1194

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

IS - 8

ER -

Hemojuvelin modulates iron stress during acute kidney injury: Improved by furin inhibitor

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