Effect of celastrol on the progression of polycystic kidney disease in a Pkd1-deficient mouse model

Publication date: 1 November 2018Source: Life Sciences, Volume 212Author(s): Ming-Yang Chang, Chun-Yih Hsieh, Chan-Yu Lin, Tai-Di Chen, Huang-Yu Yang, Kuan-Hsing Chen, Hsiang-Hao Hsu, Ya-Chung Tian, Yung-Chang Chen, Cheng-Chieh Hung, Chih-Wei YangAbstractAimsCelastrol, a naturally occurring pentacyclic triterpene, has attracted considerable interest because it exhibits potent anti-inflammatory and anti-tumor properties. However, the effects of celastrol in autosomal dominant polycystic kidney disease (ADPKD) remain uninvestigated.Main methodsWe determined the effects of celastrol on ADPKD progression in a novel Pkd1-hypomorphic mouse model by intraperitoneal injection (postnatal day 35–63).Key findingsPkd1 miRNA transgenic (Pkd1 miR TG) mice treated with 1 mg/kg/day of celastrol exhibited a lower renal cystic index (by 21.5%) than the vehicle-treated controls, but the fractional kidney weights and blood urea nitrogen levels were not significantly affected with celastrol treatment. At a high dose (2 mg/kg/day), celastrol caused marginal weight loss in the treated mice and had no significant effect on renal cystogenesis, thus indicating a potential toxic effect. We further identified that celastrol increased the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK) in the cystic kidneys. Moreover, celastrol reduced the renal mRNA expression levels of tumor necrosis factor-α, interleukin-1β, P2RX7, F4/80, CD68, transforming growth factor-β, co...
Source: Life Sciences - Category: Biology Source Type: research