Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis
Abstract Background Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism. Methods Male Sprague–Dawley rats were infused with 20 mL of...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-10-01
|
Series: | BMC Complementary and Alternative Medicine |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12906-019-2702-6 |
id |
doaj-ba5762a5ca8b45acb8663b768eefe87c |
---|---|
record_format |
Article |
spelling |
doaj-ba5762a5ca8b45acb8663b768eefe87c2020-11-25T03:36:37ZengBMCBMC Complementary and Alternative Medicine1472-68822019-10-0119111110.1186/s12906-019-2702-6Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysisJun-Li Zhao0Ting Zhang1Xia Shao2Jun-Jun Zhu3Mei-Zi Guo4Department of Nephrology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu HospitalDepartment of Nephrology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu HospitalDepartment of Nephrology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu HospitalDepartment of Nephrology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu HospitalDepartment of Geriatrics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu HospitalAbstract Background Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism. Methods Male Sprague–Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson’s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA. Results Compared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-β1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-β1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-β1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin. Conclusions Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.http://link.springer.com/article/10.1186/s12906-019-2702-6Peritoneal dialysis (PD)Peritoneal fibrosis (PF)CurcuminTransforming growth factor-activated kinase-1 (TAK1)Epithelial-mesenchymal transition (EMT) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun-Li Zhao Ting Zhang Xia Shao Jun-Jun Zhu Mei-Zi Guo |
spellingShingle |
Jun-Li Zhao Ting Zhang Xia Shao Jun-Jun Zhu Mei-Zi Guo Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis BMC Complementary and Alternative Medicine Peritoneal dialysis (PD) Peritoneal fibrosis (PF) Curcumin Transforming growth factor-activated kinase-1 (TAK1) Epithelial-mesenchymal transition (EMT) |
author_facet |
Jun-Li Zhao Ting Zhang Xia Shao Jun-Jun Zhu Mei-Zi Guo |
author_sort |
Jun-Li Zhao |
title |
Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis |
title_short |
Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis |
title_full |
Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis |
title_fullStr |
Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis |
title_full_unstemmed |
Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis |
title_sort |
curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (tak1) pathway in a rat model of peritoneal dialysis |
publisher |
BMC |
series |
BMC Complementary and Alternative Medicine |
issn |
1472-6882 |
publishDate |
2019-10-01 |
description |
Abstract Background Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism. Methods Male Sprague–Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson’s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA. Results Compared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-β1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-β1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-β1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin. Conclusions Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin. |
topic |
Peritoneal dialysis (PD) Peritoneal fibrosis (PF) Curcumin Transforming growth factor-activated kinase-1 (TAK1) Epithelial-mesenchymal transition (EMT) |
url |
http://link.springer.com/article/10.1186/s12906-019-2702-6 |
work_keys_str_mv |
AT junlizhao curcuminamelioratesperitonealfibrosisviainhibitionoftransforminggrowthfactoractivatedkinase1tak1pathwayinaratmodelofperitonealdialysis AT tingzhang curcuminamelioratesperitonealfibrosisviainhibitionoftransforminggrowthfactoractivatedkinase1tak1pathwayinaratmodelofperitonealdialysis AT xiashao curcuminamelioratesperitonealfibrosisviainhibitionoftransforminggrowthfactoractivatedkinase1tak1pathwayinaratmodelofperitonealdialysis AT junjunzhu curcuminamelioratesperitonealfibrosisviainhibitionoftransforminggrowthfactoractivatedkinase1tak1pathwayinaratmodelofperitonealdialysis AT meiziguo curcuminamelioratesperitonealfibrosisviainhibitionoftransforminggrowthfactoractivatedkinase1tak1pathwayinaratmodelofperitonealdialysis |
_version_ |
1724549154990981120 |