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

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.

SUBMITTER: Leuenroth SJ

PROVIDER: S-EPMC1838612 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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

Leuenroth Stephanie J SJ Okuhara Dayne D Shotwell Joseph D JD Markowitz Glen S GS Yu Zhiheng Z Somlo Stefan S Crews Craig M CM

Proceedings of the National Academy of Sciences of the United States of America 20070306 11

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 of ...[more]

PMID: 17360534

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Project description:Background:Traditional, complementary, and alternative medicine (TCAM) has attracted increasing attention in developed countries, but its mainstream status in China, the home of TCAM, is unclear. Over the period of 2004-2016, we analyze the health resources and health resource utilization of traditional medicine in traditional Chinese medicine (TCM) hospitals in China. Methods:Over 2004-2016, we obtained data from all TCM hospitals in all Chinese provinces to create a hospital-based, longitudinal dataset. TCM health resources and their utilization were measured by two outcome variables: (1) primary outcome variables comprising the proportion of TCM physicians, TCM pharmacists, revenue from TCM drugs, and TCM prescriptions and (2) the secondary outcome variables, as proxies of westernization for TCM hospitals, comprising the number of medical equipment above RMB 10,000 and the proportion of surgery in inpatient visits. We used linear regression models with hospital-fixed effects to analyze time trends for the outcome variables. Results:The number of public TCM hospitals remained stable from 2004 to 2016, while the number of private TCM hospitals increased from 294 in 2004 to 1560 in 2016. There was a small percentage increase in the proportion of TCM physicians (0.280%), TCM pharmacists (0.298%), and revenue from Chinese medicines (0.331%) and TCM prescriptions (1.613%) per hospital per year. Chinese drugs accounted for less than a half of the total drug prescriptions, and accordingly, just one-third of the drug revenue was from Chinese medicines at TCM hospitals. The proportions of physicians, pharmacists, revenue from Chinese drug sales, and traditional medicine prescriptions never reach the 60% benchmark target for mainstream in TCM hospitals. As proxies for Western medicine practices in TCM hospitals, the number of medical equipment above RMB 10,000 rapidly rose by over 13 percent per hospital per year, but the proportion of inpatient surgeries declined by 0.830 percentage points per hospital per year, reflecting a mixed trend in the use of Western medicine practices. Conclusion:For the 2004-2016 period, traditional medicine, although making progress towards the mainstream benchmark of 60% TCM services, was still not mainstream at TCM hospitals.

Dataset Information

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

Publications

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

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