First Author | Zhou H | Year | 2012 |
Journal | Am J Physiol Renal Physiol | Volume | 302 |
Issue | 10 | Pages | F1234-42 |
PubMed ID | 22338085 | Mgi Jnum | J:184731 |
Mgi Id | MGI:5426125 | Doi | 10.1152/ajprenal.00356.2011 |
Citation | Zhou H, et al. (2012) Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models. Am J Physiol Renal Physiol 302(10):F1234-42 |
abstractText | Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by massive enlargement of fluid-filled cysts in the kidney. However, there is no effective therapy yet for this disease. To examine whether ginkgolide B, a natural compound, inhibits cyst development, a Madin-Darby canine kidney (MDCK) cyst model, an embryonic kidney cyst model, and a PKD mouse model were used. Interestingly, ginkgolide B significantly inhibited MDCK cyst formation dose dependently, with up to 69% reduction by 2 muM ginkgolide B. Ginkgolide B also significantly inhibited cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse model. To determine the underlying mechanisms, the effect of ginkgolide B on MDCK cell viability, proliferation, apoptosis, chloride transporter CFTR activity, and intracellular signaling pathways were also studied. Ginkgolide B did not affect cell viability, proliferation, and expression and activity of the chloride transporter CFTR that mediates cyst fluid secretion. Ginkgolide B induced cyst cell differentiation and altered the Ras/MAPK signaling pathway. Taken together, our results demonstrate that ginkgolide B inhibits renal cyst formation and enlargement, suggesting that ginkgolide B might be developed into a novel candidate drug for ADPKD. |