Parthenolide, an NF-κB inhibitor, alleviates peritoneal fibrosis by suppressing the TGF-β/Smad pathway
Parthenolide, an NF-κB inhibitor, alleviates peritoneal fibrosis by suppressing the TGF-β/Smad pathway
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小白菊内酯 (Parthenolide) 是一种 NF-κ B 抑制剂，通过抑制 TGF-β/Smad 通路减轻腹膜纤维化
DOI：
10.1016/j.intimp.2019.106064
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Long, Haibo
中科院分区：
文献类型：
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作者：
Zhang, Ying;Huang, Qianyin;Long, Haibo
转化生长因子（TGF）-β/Smad信号在腹膜透析（PD）相关腹膜纤维化的发病机制中起着重要作用。银胶菊（PTL）是一种天然存在的植物化学物质，从小白菊（Tanacetum parthenium）的芽中分离得到，具有镇痛、抗炎和抗癌活性。在这项研究中，我们研究了PTL对PD相关腹膜纤维化的治疗潜力，所述PD相关腹膜纤维化是通过每天腹腔内注射4.25%的含海藻糖的PD流体（PDF）在体内和TGF-β 1诱导的上皮-间质转化（EMT）在体外诱导的。在PDF注射前或PDF注射14天后每天给予PTL。两种PTL治疗均显示出对腹膜纤维化的保护作用并预防腹膜功能障碍。类似地，PTL抑制TGF-β 1处理的HMrSV 5细胞中纤维化标记物（纤连蛋白和胶原I）的表达，并恢复上皮标记物（E-钙粘蛋白）的表达。此外，PTL抑制TGF-β 1诱导的Smad 2和Smad 3磷酸化和核转位，但不影响Smad 1/5/9磷酸化或激活TGF-β 1的其他下游信号通路，包括AKT，细胞外信号调节激酶（ERK）或p38。总之，PTL治疗通过抑制TGF-β/Smad通路可能代表了PD相关腹膜纤维化的有效和新型疗法。
Transforming growth factor (TGF)-beta/Smad signalling plays a central role in the pathogenesis of peritoneal fibrosis related to peritoneal dialysis (PD). Parthenolide (PTL), a naturally occurring phytochemical, is isolated from the shoots of feverfew (Tanacetum parthenium) and displays analgesia, anti-inflammation and anticancer activities. In this study, we examined the therapeutic potential of PTL on PD-related peritoneal fibrosis induced by daily intraperitoneal injection of 4.25% dextrose-containing PD fluid (PDF) in vivo and TGF-beta 1-induced epithelial-mesenchymal transition (EMT) in vitro. PTL was administered daily before PDF injection or after 14 days of PDF injection. Both PTL treatments showed a protective effect on peritoneal fibrosis and prevented peritoneal dysfunction. Similarly, PTL suppressed the expression of fibrotic markers (fibronectin and collagen I) and restored the expression of the epithelial marker (E-cadherin) in TGF-beta 1-treated HMrSV5 cells. Furthermore, PTL inhibited TGF-beta 1-induced Smad2 and Smad3 phosphorylation and nuclear translocation but did not influence Smad1/5/9 phosphorylation or activate other downstream signalling pathways of TGF-beta 1, including AKT, extracellular signal-regulated kinase (ERK) or p38. In conclusion, PTL treatment may represent an effective and novel therapy for PD-associated peritoneal fibrosis by suppressing the TGF-beta/Smad pathway.