马兜铃酸
肾脏疾病
SMAD公司
上皮-间质转换
肾功能
癌症研究
MAPK/ERK通路
纤维化
肾
医学
化学
药理学
胱抑素C
信号转导
内分泌学
转化生长因子
内科学
生物
癌症
生物化学
遗传学
转移
作者
Jia‐Feng Chang,Chih‐Yu Hsieh,Kuo‐Cheng Lu,Yue-Wen Chen,Shih‐Shin Liang,Chih-Cheng Lin,Chi‐Feng Hung,Jian-Chiun Liou,Mai-Szu Wu
出处
期刊:Toxins
[Multidisciplinary Digital Publishing Institute]
日期:2020-06-02
卷期号:12 (6): 364-364
被引量:19
标识
DOI:10.3390/toxins12060364
摘要
The nephrotoxicity of aristolochic acids (AAs), p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were well-documented, culminating in tubulointerstitial fibrosis (TIF), advanced chronic kidney disease (CKD) and fatal urothelial cancer. Nonetheless, information regarding the attenuation of AAs-induced nephropathy (AAN) and uremic toxin retention is scarce. Propolis is a versatile natural product, exerting anti-oxidant, anti-cancer and anti-fibrotic properties. We aimed to evaluate nephroprotective effects of propolis extract (PE) in a murine model. AAN was developed to retain circulating PCS and IS using C57BL/6 mice, mimicking human CKD. The kidney sizes/masses, renal function indicators, plasma concentrations of PCS/IS, tissue expressions of TIF, α-SMA, collagen IaI, collagen IV and signaling pathways in transforming growth factor-β (TGF-β) family were analyzed among the control, PE, AAN, and AAN-PE groups. PE ameliorated AAN-induced renal atrophy, renal function deterioration, TIF, plasma retention of PCS and IS. PE also suppressed α-SMA expression and deposition of collagen IaI and IV in the fibrotic epithelial-mesenchymal transition. Notably, PE treatment in AAN model inhibited not only SMAD 2/3-dependent pathways but also SMAD-independent JNK/ERK activation in the signaling cascades of TGF-β family. Through disrupting fibrotic epithelial-mesenchymal transition and TGF-β signaling transduction pathways, PE improves TIF and thereby facilitates renal excretion of PCS and IS in AAN. In light of multi-faced toxicity of AAs, PE may be capable of developing a new potential drug to treat CKD patients exposed to AAs.
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