The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Triptolide is a traditional Chinese medicine-derived inhibitor of polycystic kidney disease
Open accessAbstract
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.
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Cites
Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells
Nauli, S. M., Alenghat, F. J., Luo, Y., Williams, E., Vassilev, P., Li, X., Elia, A. E. H., Lu, W., Brown, E. M., Quinn, S. J., et al. (2003) · Nature Genetics · doi:10.1038/ng1076 · Cited by 2,057
Yoder, B. K., Hou, X., & Guay-Woodford, L. M. (2002) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000029587.47950.25 · Cited by 935
A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans
Barr, M. M., & Sternberg, P. W. (1999) · Nature · doi:10.1038/43913 · Cited by 541
Qiu, D., & Kao, P. N. (2003) · Drugs in R & D · doi:10.2165/00126839-200304010-00001 · Cited by 311
Cited by
Autosomal dominant polycystic kidney disease
Torres, V. E., Harris, P. C., & Pirson, Y. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60601-1 · Cited by 1,550
Harris, P. C., & Torres, V. E. (2009) · Annual Review of Medicine · doi:10.1146/annurev.med.60.101707.125712 · Cited by 801
Inhibiting eukaryotic transcription: which compound to choose? How to evaluate its activity
Bensaude, O. (2011) · Transcription · doi:10.4161/trns.2.3.16172 · Cited by 574
Triptolide: Progress on research in pharmacodynamics and toxicology
Li, X.-J., Jiang, Z.-Z., & Zhang, L.-Y. (2014) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2014.06.006 · Cited by 378
Transient receptor potential (TRP) channels: a clinical perspective
Kaneko, Y., & Szallasi, A. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12414 · Cited by 370
Metadata
- Authors
- Leuenroth, S. J., Okuhara, D., Shotwell, J. D., Markowitz, G. S., Yu, Z., Somlo, S., & Crews, C. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-03-13
- Volume
- 104
- Issue
- 11
- Pages
- 4389-4394
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2102570939
- Cited by
- 236
- References
- 4
- FWCI
- 9.71
- Type
- journal article
- Language
- en
- Open access
- green
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