Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 78, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2019.106064
Keywords
Parthenolide; Peritoneal fibrosis; TGF-beta 1; Smad
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81673792, 81600624, 81704134, 81873346, 81800612, U1801288, 81900607]
- Natural Science Foundation of Guangdong Province, China [2017A030313708]
- Science and Technology Planning Project of Guangdong Province, China [2017A020215158]
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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.
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