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Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseasescharacterized 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 cystdevelopment.Using an in vitro MDCK cystogenesis model,we identified ganoderic acid A (GA-A) as the most promising candidateamong the 12 ganoderic acid (GA) monomers.We further showed that GA-A (6.25-100 μM) significantly inhibited cyst growth inMDCK cyst model and embryonic kidney cyst model in vitro,and the inhibitory effect was reversible.In kidney-specific Pkd1knockout (kPKD) mice displaying severe cystic kidney disease,administration of GA-A (50 mg· kg-1 ·d-1,sc) significantly attenuatedrenal cyst development.In both MDCK cells and kidney of kPKD mice,we revealed that GA-A dose-dependently downregulated theRas/MAPK signaling pathway.The expression of proliferating cell nuclear antigen (PCNA) was also suppressed,suggesting apossible effect of GA-A on cell proliferation.These experimental data suggest that GA-A may be the main ingredient of GT as apotential therapeutic reagent for treating ADPKD.