| First Author | Wang E | Year | 2017 |
| Journal | Kidney Int | Volume | 91 |
| Issue | 2 | Pages | 412-422 |
| PubMed ID | 28341240 | Mgi Jnum | J:329491 |
| Mgi Id | MGI:6859608 | Doi | 10.1016/j.kint.2016.09.005 |
| Citation | Wang E, et al. (2017) Overexpression of exogenous kidney-specific Ngal attenuates progressive cyst development and prolongs lifespan in a murine model of polycystic kidney disease. Kidney Int 91(2):412-422 |
| abstractText | 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/L3) (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. |
