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Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway

Mesangial proliferative glomerulonephritis (MPGN) is the most common type of chronic kidney disease in China, characterized by mesangial cell proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Radix Paeoniae Alba, has been used for various kinds of kidney...

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Autores principales: Liu, Bihao, Lin, Jin, Bai, Lixia, Zhou, Yuan, Lu, Ruirui, Zhang, Peichun, Chen, Dandan, Li, Honglian, Song, Jianping, Liu, Xusheng, Wu, Yifan, Wu, Junbiao, Liang, Chunling, Zhou, Jiuyao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745507/
https://www.ncbi.nlm.nih.gov/pubmed/31551783
http://dx.doi.org/10.3389/fphar.2019.00978
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author Liu, Bihao
Lin, Jin
Bai, Lixia
Zhou, Yuan
Lu, Ruirui
Zhang, Peichun
Chen, Dandan
Li, Honglian
Song, Jianping
Liu, Xusheng
Wu, Yifan
Wu, Junbiao
Liang, Chunling
Zhou, Jiuyao
author_facet Liu, Bihao
Lin, Jin
Bai, Lixia
Zhou, Yuan
Lu, Ruirui
Zhang, Peichun
Chen, Dandan
Li, Honglian
Song, Jianping
Liu, Xusheng
Wu, Yifan
Wu, Junbiao
Liang, Chunling
Zhou, Jiuyao
author_sort Liu, Bihao
collection PubMed
description Mesangial proliferative glomerulonephritis (MPGN) is the most common type of chronic kidney disease in China, characterized by mesangial cell proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Radix Paeoniae Alba, has been used for various kinds of kidney diseases. However, there are no studies reporting the effects of paeoniflorin on MPGN. The present study aims to investigate whether paeoniflorin plays a role in MPGN and confirm the underlying molecular mechanisms. Our results manifested that paeoniflorin strongly restrained 24 h urinary protein and promoted renal function and dyslipidemia in a MPGN rat model. Moreover, paeoniflorin attenuated mesangial cell proliferation and inflammation both in MPGN rats and human mesangial cells (HMCs) treated with lipopolysaccharide (LPS). In detail, paeoniflorin decreased the number of mesangial cells and expressions of proliferation marker Ki67 in MPGN rats. Paeoniflorin also inhibited HMC proliferation and blocked cell cycle progression. In addition, the contents of inflammatory factors and the expressions of macrophage marker iNOS were decreased after paeoniflorin treatment. Furthermore, we found that the protective effect of paeoniflorin was accompanied by a strong inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β pathway. Paeoniflorin enhanced the inhibitory effect of PI3K inhibitor LY294002 and suppressed the activated effect of PI3K agonist insulin-like growth factor 1 (IGF-1) on PI3K/AKT/GSK-3β pathway. In conclusion, these results demonstrated that paeoniflorin ameliorates MPGN by inhibiting mesangial cell proliferation and inflammatory response through the PI3K/AKT/GSK-3β pathway.
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spelling pubmed-67455072019-09-24 Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway Liu, Bihao Lin, Jin Bai, Lixia Zhou, Yuan Lu, Ruirui Zhang, Peichun Chen, Dandan Li, Honglian Song, Jianping Liu, Xusheng Wu, Yifan Wu, Junbiao Liang, Chunling Zhou, Jiuyao Front Pharmacol Pharmacology Mesangial proliferative glomerulonephritis (MPGN) is the most common type of chronic kidney disease in China, characterized by mesangial cell proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Radix Paeoniae Alba, has been used for various kinds of kidney diseases. However, there are no studies reporting the effects of paeoniflorin on MPGN. The present study aims to investigate whether paeoniflorin plays a role in MPGN and confirm the underlying molecular mechanisms. Our results manifested that paeoniflorin strongly restrained 24 h urinary protein and promoted renal function and dyslipidemia in a MPGN rat model. Moreover, paeoniflorin attenuated mesangial cell proliferation and inflammation both in MPGN rats and human mesangial cells (HMCs) treated with lipopolysaccharide (LPS). In detail, paeoniflorin decreased the number of mesangial cells and expressions of proliferation marker Ki67 in MPGN rats. Paeoniflorin also inhibited HMC proliferation and blocked cell cycle progression. In addition, the contents of inflammatory factors and the expressions of macrophage marker iNOS were decreased after paeoniflorin treatment. Furthermore, we found that the protective effect of paeoniflorin was accompanied by a strong inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β pathway. Paeoniflorin enhanced the inhibitory effect of PI3K inhibitor LY294002 and suppressed the activated effect of PI3K agonist insulin-like growth factor 1 (IGF-1) on PI3K/AKT/GSK-3β pathway. In conclusion, these results demonstrated that paeoniflorin ameliorates MPGN by inhibiting mesangial cell proliferation and inflammatory response through the PI3K/AKT/GSK-3β pathway. Frontiers Media S.A. 2019-09-09 /pmc/articles/PMC6745507/ /pubmed/31551783 http://dx.doi.org/10.3389/fphar.2019.00978 Text en Copyright © 2019 Liu, Lin, Bai, Zhou, Lu, Zhang, Chen, Li, Song, Liu, Wu, Wu, Liang and Zhou http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Liu, Bihao
Lin, Jin
Bai, Lixia
Zhou, Yuan
Lu, Ruirui
Zhang, Peichun
Chen, Dandan
Li, Honglian
Song, Jianping
Liu, Xusheng
Wu, Yifan
Wu, Junbiao
Liang, Chunling
Zhou, Jiuyao
Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway
title Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway
title_full Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway
title_fullStr Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway
title_full_unstemmed Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway
title_short Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway
title_sort paeoniflorin inhibits mesangial cell proliferation and inflammatory response in rats with mesangial proliferative glomerulonephritis through pi3k/akt/gsk-3β pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745507/
https://www.ncbi.nlm.nih.gov/pubmed/31551783
http://dx.doi.org/10.3389/fphar.2019.00978
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