Format

Send to

Choose Destination
See comment in PubMed Commons below
J Am Soc Nephrol. 2008 Sep;19(9):1659-62. doi: 10.1681/ASN.2008030259. Epub 2008 Jul 23.

Triptolide reduces cystogenesis in a model of ADPKD.

Author information

1
Yale University, Department MCD Biology, P.O. Box 208103, New Haven, CT 06520-8103, USA.

Abstract

Mutations in PKD1 result in autosomal dominant polycystic kidney disease, which is characterized by increased proliferation of tubule cells leading to cyst initiation and subsequent expansion. Given the cell proliferation associated with cyst growth, an attractive therapeutic strategy has been to target the hyperproliferative nature of the disease. We previously demonstrated that the small molecule triptolide induces cellular calcium release through a polycystin-2-dependent pathway, arrests Pkd1(-/-) cell growth, and reduces cystic burden in Pkd1(-/-) embryonic mice. To assess cyst progression in neonates, we used the kidney-specific Pkd1(flox/-);Ksp-Cre mouse model of autosomal dominant polycystic kidney disease, in which the burden of cysts is negligible at birth but then progresses rapidly over days. The number, size, and proliferation rate of cysts were examined. Treatment with triptolide significantly improved renal function at postnatal day 8 by inhibition of the early phases of cyst growth. Because the proliferative index of kidney epithelium in neonates versus adults is significantly different, future studies will need to address whether triptolide delays or reduces cyst progression in the Pkd1 adult model.

PMID:
18650476
PMCID:
PMC2518446
DOI:
10.1681/ASN.2008030259
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center