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Quercetin inhibits renal cyst growth in vitro and via parenteral injection in a polycystic kidney disease mouse model

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by massive enlargement of fluid-filled cysts in the kidney. There is an urgent need to develop effective ADPKD therapies. We used an in vitro Madin–Darby canine kidney (MDCK) cyst model and a murine embryonic kidney cyst model to evaluate whether quercetin inhibits cyst development. We then used a polycystic kidney disease (PKD) mouse model to further determine the in vivo effects of quercetin (100 mg per kg body weight twice per day) on PKD mice via subcutaneous injections. The results show that quercetin significantly and dose-dependently inhibited cyst formation and enlargement in the MDCK cyst and embryonic kidney cyst models. Quercetin also noticeably reduced the cystic index in PKD mice. Furthermore, the effective dose of quercetin did not cause cytotoxicity in MDCK cells. Quercetin treatment decreased the levels of intracellular signalling proteins in PKD mouse kidneys, including phosphorylated protein kinase B (also known as AKT) and phosphorylated extracellular signal-regulated kinase (ERK), which are upregulated and promote cyst development in ADPKD. Quercetin also reversed E-cadherin expression, which is localized in normal proximal tubules in PKD mouse kidneys. Taken together, these results demonstrate that quercetin hinders renal cyst development in vivo and in vitro and represents a novel candidate strategy for the treatment of ADPKD.

Graphical abstract: Quercetin inhibits renal cyst growth in vitro and via parenteral injection in a polycystic kidney disease mouse model

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Publication details

The article was received on 15 Aug 2017, accepted on 23 Nov 2017 and first published on 28 Nov 2017


Article type: Paper
DOI: 10.1039/C7FO01253E
Citation: Food Funct., 2018, Advance Article
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    Quercetin inhibits renal cyst growth in vitro and via parenteral injection in a polycystic kidney disease mouse model

    Y. Zhu, T. Teng, H. Wang, H. Guo, L. Du, B. Yang, X. Yin and Y. Sun, Food Funct., 2018, Advance Article , DOI: 10.1039/C7FO01253E

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