41 80

Cited 0 times in

Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

Authors
 Yohan Seo  ;  Chin Hee Mun  ;  So-Hyeon Park  ;  Dongkyu Jeon  ;  Su Jeong Kim  ;  Taejun Yoon  ;  Eunhee Ko  ;  Sungwoo Jo  ;  Yong-Beom Park  ;  Wan Namkung  ;  Sang-Won Lee 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.21(14) : 4975, 2020-07 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 
Issue Date
2020-07
Keywords
NZB/W F1 mice ; PAR2 ; lupus nephritis ; podocyte ; punicalagin ; systemic lupus erythematosus
Abstract
Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 ± 0.03 µM) and significantly reduced the PAR2-mediated activation of ERK1/2 and NF-κB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-γ, and TNF-α expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.
Files in This Item:
T202002512.pdf Download
DOI
10.3390/ijms21144975
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Mun, Chin Hee(문진희)
Park, Yong Beom(박용범)
Lee, Sang-Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179533
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links