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Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseases characterized by progressive enlargement of fluid-filled renal cysts. Our previous study has shown that Ganoderma triterpenes (GT) retards PKD renal cyst development. In the present s...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Singapore
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468358/ https://www.ncbi.nlm.nih.gov/pubmed/31911637 http://dx.doi.org/10.1038/s41401-019-0329-2 |
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author | Meng, Jia Sai-zhen Wang He, Jin-zhao Zhu, Shuai Huang, Bo-yue Wang, Shu-yuan Li, Min Zhou, Hong Lin, Shu-qian Yang, Bao-xue |
author_facet | Meng, Jia Sai-zhen Wang He, Jin-zhao Zhu, Shuai Huang, Bo-yue Wang, Shu-yuan Li, Min Zhou, Hong Lin, Shu-qian Yang, Bao-xue |
author_sort | Meng, Jia |
collection | PubMed |
description | Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseases characterized by progressive enlargement of fluid-filled renal cysts. Our previous study has shown that Ganoderma triterpenes (GT) retards PKD renal cyst development. In the present study we identified the effective ingredient of GT in suppression of kidney cyst development. Using an in vitro MDCK cystogenesis model, we identified ganoderic acid A (GA-A) as the most promising candidate among the 12 ganoderic acid (GA) monomers. We further showed that GA-A (6.25−100 μM) significantly inhibited cyst growth in MDCK cyst model and embryonic kidney cyst model in vitro, and the inhibitory effect was reversible. In kidney-specific Pkd1 knockout (kPKD) mice displaying severe cystic kidney disease, administration of GA-A (50 mg· kg(−1) ·d(−1), sc) significantly attenuated renal cyst development. In both MDCK cells and kidney of kPKD mice, we revealed that GA-A dose-dependently downregulated the Ras/MAPK signaling pathway. The expression of proliferating cell nuclear antigen (PCNA) was also suppressed, suggesting a possible effect of GA-A on cell proliferation. These experimental data suggest that GA-A may be the main ingredient of GT as a potential therapeutic reagent for treating ADPKD. |
format | Online Article Text |
id | pubmed-7468358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Singapore |
record_format | MEDLINE/PubMed |
spelling | pubmed-74683582020-09-03 Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease Meng, Jia Sai-zhen Wang He, Jin-zhao Zhu, Shuai Huang, Bo-yue Wang, Shu-yuan Li, Min Zhou, Hong Lin, Shu-qian Yang, Bao-xue Acta Pharmacol Sin Article Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseases characterized by progressive enlargement of fluid-filled renal cysts. Our previous study has shown that Ganoderma triterpenes (GT) retards PKD renal cyst development. In the present study we identified the effective ingredient of GT in suppression of kidney cyst development. Using an in vitro MDCK cystogenesis model, we identified ganoderic acid A (GA-A) as the most promising candidate among the 12 ganoderic acid (GA) monomers. We further showed that GA-A (6.25−100 μM) significantly inhibited cyst growth in MDCK cyst model and embryonic kidney cyst model in vitro, and the inhibitory effect was reversible. In kidney-specific Pkd1 knockout (kPKD) mice displaying severe cystic kidney disease, administration of GA-A (50 mg· kg(−1) ·d(−1), sc) significantly attenuated renal cyst development. In both MDCK cells and kidney of kPKD mice, we revealed that GA-A dose-dependently downregulated the Ras/MAPK signaling pathway. The expression of proliferating cell nuclear antigen (PCNA) was also suppressed, suggesting a possible effect of GA-A on cell proliferation. These experimental data suggest that GA-A may be the main ingredient of GT as a potential therapeutic reagent for treating ADPKD. Springer Singapore 2020-01-07 2020-06 /pmc/articles/PMC7468358/ /pubmed/31911637 http://dx.doi.org/10.1038/s41401-019-0329-2 Text en © CPS and SIMM 2019 |
spellingShingle | Article Meng, Jia Sai-zhen Wang He, Jin-zhao Zhu, Shuai Huang, Bo-yue Wang, Shu-yuan Li, Min Zhou, Hong Lin, Shu-qian Yang, Bao-xue Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease |
title | Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease |
title_full | Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease |
title_fullStr | Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease |
title_full_unstemmed | Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease |
title_short | Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease |
title_sort | ganoderic acid a is the effective ingredient of ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468358/ https://www.ncbi.nlm.nih.gov/pubmed/31911637 http://dx.doi.org/10.1038/s41401-019-0329-2 |
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