Overexpression of DJ-1 alleviates autosomal dominant polycystic kidney disease by regulating cell proliferation, apoptosis, and mitochondrial metabolism and .

BACKGROUND

is critical for the mitochondrial function associated with autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate 's function in the pathogenesis of ADPKD.

METHODS

was knocked-down in IMCD3 cells to evaluate the effects of on cell phenotype and mitochondrial function . Furthermore, we generated three groups of mice with different expression levels of DJ-1 within an established ADPKD model: ADPKD, ADPKD, and ADPKD.

RESULTS

knock-down significantly increased oxidative stress as well as the proliferation and apoptosis rate of IMCD3 cells, along with Bcl-2 down-regulation and the up-regulation of Ki67, PCNA, Bax, cleaved caspase-3, and cleaved caspase-9. knock-down suppressed the cellular respiration, Ca absorption, and mitochondrial complex I activity in mitochondria. , we verified that DJ-1 was down-regulated in ADPKD models, and its overexpression attenuated the renal dysfunction in ADPKD models. The transgenic mice had a significantly smaller renal cyst and less interstitial fibrosis than control, accompanied byα-SMA, fibronectin, and TGF-β1 up-regulation. Moreover, results confirmed DJ-1 overexpression inhibited the proliferation and apoptosis of tubular epithelial cells along with down-regulation of Ki67, PCNA, p53, intracellular Cyt c, cleaved caspase-3, and cleaved caspase-9 and the up-regulation of Bcl-2.

CONCLUSIONS

DJ-1 was down-regulated in ADPKD models, and its overexpression may attenuate the renal dysfunction and pathological damage by regulating the proliferation, apoptosis, oxidative stress and mitochondrial metabolism, which may be mediated by the p53 signaling pathway.