期刊
KIDNEY INTERNATIONAL
卷 91, 期 2, 页码 412-422出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2016.09.005
关键词
cysts; neutrophil gelatinase-associated lipocalin; Pkd1
资金
- National Laboratory Animal Center (NLAC) [104-2-1-1]
- Ministry of Science and Technology [104-2325-B-003-003]
- Taiwan Protein Project [MOST 105-0210-01-12-01]
- NLAC
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 (Pkd1(L3/L3)): Pkd1(L3/L)3 (with endogenous Ngal), Pkd1(L3/L3); Ngal(Tg/Tg) (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1(L3/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 alpha-smooth muscle actin, hypoxia-inducible factor 1-alpha, 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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