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Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4389-94. Epub 2007 Mar 6.

Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease.

Author information

1
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.

Abstract

During kidney organogenesis, tubular epithelial cells proliferate until a functional tubule is formed as sensed by cilia bending in response to fluid flow. This flow-induced ciliary mechanosensation opens the calcium (Ca(2+)) channel polycystin-2 (PC2), resulting in a calcium flux-mediated cell cycle arrest. Loss or mutation of either PC2 or its regulatory protein polycystin-1 (PC1) results in autosomal dominant polycystic kidney disease (ADPKD), characterized by cyst formation and growth and often leading to renal failure and death. Here we show that triptolide, the active diterpene in the traditional Chinese medicine Lei Gong Teng, induces Ca(2+) release by a PC2-dependent mechanism. Furthermore, in a murine model of ADPKD, triptolide arrests cellular proliferation and attenuates overall cyst formation by restoring Ca(2+) signaling in these cells. We anticipate that small molecule induction of PC2-dependent calcium release is likely to be a valid therapeutic strategy for ADPKD.

PMID:
17360534
PMCID:
PMC1838612
DOI:
10.1073/pnas.0700499104
[Indexed for MEDLINE]
Free PMC Article

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