Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease

Ellian Wang, Yuan Yow Chiou, Wen Yih Jeng, Hsiu Kuan Lin, Hsi Hui Lin, Hsian Jean Chin, Chi Kuang Leo Wang, Shang Shiuan Yu, Shih Chieh Tsai, Chih Ying Chiang, Po Hao Cheng, Hong Jie Lin, Si Tse Jiang, Sou Tyau Chiu, Hsiu Mei Hsieh-Li

研究成果: Article

3 引文 (Scopus)

摘要

Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an established PKD model (Pkd1L3/L3): Pkd1L3/L3 (with endogenous Ngal), Pkd1L3/L3; NgalTg/Tg (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1L3/L3; Ngal-/- mice (with Ngal deficiency). Knockout of endogenous Ngal had no effect on phenotypes, cystic progression, or survival of the PKD mice. However, the transgenic mice had a significantly longer lifespan, smaller (but not fewer) renal cysts, and less interstitial fibrosis than the mice without or with endogenous Ngal. Western-blot analyses showed significant increases in Ngal and cleaved caspase-3 and decreases in α-smooth muscle actin, hypoxia-inducible factor 1-α, pro-caspase 3, proliferating cell nuclear antigen, Akt, mammalian target of rapamycin, and S6 Kinase in the transgenic mice as compared with the other 2 strains of PKD mice. Thus, overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in PKD mice, was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis.

原文English
頁(從 - 到)412-422
頁數11
期刊Kidney international
91
發行號2
DOIs
出版狀態Published - 2017 二月 1

指紋

Polycystic Kidney Diseases
Cysts
Kidney
Caspase 3
Transgenic Mice
Fibrosis
Lipocalin-2
Ribosomal Protein S6 Kinases
Autosomal Dominant Polycystic Kidney
Hypoxia-Inducible Factor 1
Proliferating Cell Nuclear Antigen
Sirolimus
Acute Kidney Injury
Smooth Muscle
Disease Progression
Actins
Biomarkers
Western Blotting

All Science Journal Classification (ASJC) codes

  • Nephrology

引用此文

Wang, Ellian ; Chiou, Yuan Yow ; Jeng, Wen Yih ; Lin, Hsiu Kuan ; Lin, Hsi Hui ; Chin, Hsian Jean ; Leo Wang, Chi Kuang ; Yu, Shang Shiuan ; Tsai, Shih Chieh ; Chiang, Chih Ying ; Cheng, Po Hao ; Lin, Hong Jie ; Jiang, Si Tse ; Chiu, Sou Tyau ; Hsieh-Li, Hsiu Mei. / Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease. 於: Kidney international. 2017 ; 卷 91, 編號 2. 頁 412-422.
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title = "Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease",
abstract = "Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an established PKD model (Pkd1L3/L3): Pkd1L3/L3 (with endogenous Ngal), Pkd1L3/L3; NgalTg/Tg (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1L3/L3; Ngal-/- mice (with Ngal deficiency). Knockout of endogenous Ngal had no effect on phenotypes, cystic progression, or survival of the PKD mice. However, the transgenic mice had a significantly longer lifespan, smaller (but not fewer) renal cysts, and less interstitial fibrosis than the mice without or with endogenous Ngal. Western-blot analyses showed significant increases in Ngal and cleaved caspase-3 and decreases in α-smooth muscle actin, hypoxia-inducible factor 1-α, pro-caspase 3, proliferating cell nuclear antigen, Akt, mammalian target of rapamycin, and S6 Kinase in the transgenic mice as compared with the other 2 strains of PKD mice. Thus, overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in PKD mice, was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis.",
author = "Ellian Wang and Chiou, {Yuan Yow} and Jeng, {Wen Yih} and Lin, {Hsiu Kuan} and Lin, {Hsi Hui} and Chin, {Hsian Jean} and {Leo Wang}, {Chi Kuang} and Yu, {Shang Shiuan} and Tsai, {Shih Chieh} and Chiang, {Chih Ying} and Cheng, {Po Hao} and Lin, {Hong Jie} and Jiang, {Si Tse} and Chiu, {Sou Tyau} and Hsieh-Li, {Hsiu Mei}",
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month = "2",
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Wang, E, Chiou, YY, Jeng, WY, Lin, HK, Lin, HH, Chin, HJ, Leo Wang, CK, Yu, SS, Tsai, SC, Chiang, CY, Cheng, PH, Lin, HJ, Jiang, ST, Chiu, ST & Hsieh-Li, HM 2017, 'Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease', Kidney international, 卷 91, 編號 2, 頁 412-422. https://doi.org/10.1016/j.kint.2016.09.005

Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease. / Wang, Ellian; Chiou, Yuan Yow; Jeng, Wen Yih; Lin, Hsiu Kuan; Lin, Hsi Hui; Chin, Hsian Jean; Leo Wang, Chi Kuang; Yu, Shang Shiuan; Tsai, Shih Chieh; Chiang, Chih Ying; Cheng, Po Hao; Lin, Hong Jie; Jiang, Si Tse; Chiu, Sou Tyau; Hsieh-Li, Hsiu Mei.

於: Kidney international, 卷 91, 編號 2, 01.02.2017, p. 412-422.

研究成果: Article

TY - JOUR

T1 - Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease

AU - Wang, Ellian

AU - Chiou, Yuan Yow

AU - Jeng, Wen Yih

AU - Lin, Hsiu Kuan

AU - Lin, Hsi Hui

AU - Chin, Hsian Jean

AU - Leo Wang, Chi Kuang

AU - Yu, Shang Shiuan

AU - Tsai, Shih Chieh

AU - Chiang, Chih Ying

AU - Cheng, Po Hao

AU - Lin, Hong Jie

AU - Jiang, Si Tse

AU - Chiu, Sou Tyau

AU - Hsieh-Li, Hsiu Mei

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an established PKD model (Pkd1L3/L3): Pkd1L3/L3 (with endogenous Ngal), Pkd1L3/L3; NgalTg/Tg (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1L3/L3; Ngal-/- mice (with Ngal deficiency). Knockout of endogenous Ngal had no effect on phenotypes, cystic progression, or survival of the PKD mice. However, the transgenic mice had a significantly longer lifespan, smaller (but not fewer) renal cysts, and less interstitial fibrosis than the mice without or with endogenous Ngal. Western-blot analyses showed significant increases in Ngal and cleaved caspase-3 and decreases in α-smooth muscle actin, hypoxia-inducible factor 1-α, pro-caspase 3, proliferating cell nuclear antigen, Akt, mammalian target of rapamycin, and S6 Kinase in the transgenic mice as compared with the other 2 strains of PKD mice. Thus, overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in PKD mice, was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis.

AB - Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an established PKD model (Pkd1L3/L3): Pkd1L3/L3 (with endogenous Ngal), Pkd1L3/L3; NgalTg/Tg (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1L3/L3; Ngal-/- mice (with Ngal deficiency). Knockout of endogenous Ngal had no effect on phenotypes, cystic progression, or survival of the PKD mice. However, the transgenic mice had a significantly longer lifespan, smaller (but not fewer) renal cysts, and less interstitial fibrosis than the mice without or with endogenous Ngal. Western-blot analyses showed significant increases in Ngal and cleaved caspase-3 and decreases in α-smooth muscle actin, hypoxia-inducible factor 1-α, pro-caspase 3, proliferating cell nuclear antigen, Akt, mammalian target of rapamycin, and S6 Kinase in the transgenic mice as compared with the other 2 strains of PKD mice. Thus, overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in PKD mice, was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis.

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