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Article Publish Status: FREE
Abstract Title:

Parthenolide, an NF-κB inhibitor, alleviates peritoneal fibrosis by suppressing the TGF-β/Smad pathway.

Abstract Source:

Int Immunopharmacol. 2019 Dec 12 ;78:106064. Epub 2019 Dec 12. PMID: 31838448

Abstract Author(s):

Ying Zhang, Qianyin Huang, Yihua Chen, Xuan Peng, Yuxian Wang, Shuting Li, Jiayu Wu, Congwei Luo, Wangqiu Gong, Bohui Yin, Jing Xiao, Weidong Zhou, Fenfen Peng, Haibo Long

Article Affiliation:

Ying Zhang

Abstract:

Transforming growth factor (TGF)-β/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-β1-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-β1-treated HMrSV5 cells. Furthermore, PTL inhibited TGF-β1-induced Smad2 and Smad3 phosphorylation and nuclear translocation but did not influence Smad1/5/9 phosphorylation or activate other downstream signalling pathways of TGF-β1, 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-β/Smad pathway.

Study Type : Animal Study

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