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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.

journal_name

Kidney Int

journal_title

Kidney international

authors

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

doi

10.1016/j.kint.2016.09.005

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

412-422

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(16)30488-4

journal_volume

91

pub_type

杂志文章

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