Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway

BackgroundsTo date, there are no specific drugs approved for the treatment of sepsis associated acute kidney injury (AKI). Shionone is a natural component with anti-inflammatory activity. In this study, we sought to determine the functional role of Shionone in sepsis-induced AKI.MethodsAnimal models...

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Main Authors: Biao Zhang, Yi Xue, Jin Zhao, Huojun Jiang, Jiaoli Zhu, Hao Yin, Yizhen Qiu, Aihao Hu, Lingqi Xu, Yi Song, Xin Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2021.796743/full
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author Biao Zhang
Yi Xue
Jin Zhao
Huojun Jiang
Jiaoli Zhu
Hao Yin
Yizhen Qiu
Aihao Hu
Lingqi Xu
Yi Song
Xin Wang
author_facet Biao Zhang
Yi Xue
Jin Zhao
Huojun Jiang
Jiaoli Zhu
Hao Yin
Yizhen Qiu
Aihao Hu
Lingqi Xu
Yi Song
Xin Wang
author_sort Biao Zhang
collection DOAJ
description BackgroundsTo date, there are no specific drugs approved for the treatment of sepsis associated acute kidney injury (AKI). Shionone is a natural component with anti-inflammatory activity. In this study, we sought to determine the functional role of Shionone in sepsis-induced AKI.MethodsAnimal models of AKI were constructed by cecum ligation and puncture (CLP) surgery. C57BL/6 mice were randomly assigned to the Sham, CLP, 10 mg/kg DXM, 50 mg/kg Shionone and 100 mg/kg Shionone groups. RAW264.7 treated with lipopolysaccharides (LPS) was used as an in vitro sepsis model and cells were divided into control, LPS, 1 μg/mL Shionone and 2 μg/mL Shionone groups. The pathological status was assessed by Hematoxylin-Eosin (HE) staining assay, protein expressions were detected by immunofluorescence staining and Western blot, macrophage typing was detected by flow, and the levels of pro-inflammatory factors (IL-6, IL-12, IL-1β, TNF-α) and anti-inflammatory factors (IL-10 and TGF-β) were measured using the corresponding kits.ResultsECM1 is highly expressed in tissue-infiltrating macrophages under inflammatory conditions. It has been observed that Shionone inhibits the expression of ECM1 and attenuates sepsis-induced injury in kidney and inflammatory factor levels in serum. In addition, Shionone may reduce inflammatory factor levels through the promotion of M2 macrophages by GM-CSF/STAT5/Arg1 pathway to alleviate sepsis induced inflammation in vitro.ConclusionThese findings demonstrate that Shionone can alleviate sepsis-induced AKI by promoting M2 macrophage polarization through regulating the ECM1/STAT5 pathway.
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spelling doaj.art-58b8ca52dddb4ef8b04b465b934f75452022-12-21T23:43:05ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-01-01810.3389/fmed.2021.796743796743Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 PathwayBiao Zhang0Yi Xue1Jin Zhao2Huojun Jiang3Jiaoli Zhu4Hao Yin5Yizhen Qiu6Aihao Hu7Lingqi Xu8Yi Song9Xin Wang10Department of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaDepartment of Nephrology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaDepartment of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaDepartment of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaDepartment of Nephrology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaLi Shicai School Inheritance Studio, Suzhou Hospital of Integrated Traditional and Western Medicine, Suzhou, ChinaDepartment of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaDepartment of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaDepartment of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaDepartment of Critical Care Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, ChinaLi Shicai School Inheritance Studio, Suzhou Hospital of Integrated Traditional and Western Medicine, Suzhou, ChinaBackgroundsTo date, there are no specific drugs approved for the treatment of sepsis associated acute kidney injury (AKI). Shionone is a natural component with anti-inflammatory activity. In this study, we sought to determine the functional role of Shionone in sepsis-induced AKI.MethodsAnimal models of AKI were constructed by cecum ligation and puncture (CLP) surgery. C57BL/6 mice were randomly assigned to the Sham, CLP, 10 mg/kg DXM, 50 mg/kg Shionone and 100 mg/kg Shionone groups. RAW264.7 treated with lipopolysaccharides (LPS) was used as an in vitro sepsis model and cells were divided into control, LPS, 1 μg/mL Shionone and 2 μg/mL Shionone groups. The pathological status was assessed by Hematoxylin-Eosin (HE) staining assay, protein expressions were detected by immunofluorescence staining and Western blot, macrophage typing was detected by flow, and the levels of pro-inflammatory factors (IL-6, IL-12, IL-1β, TNF-α) and anti-inflammatory factors (IL-10 and TGF-β) were measured using the corresponding kits.ResultsECM1 is highly expressed in tissue-infiltrating macrophages under inflammatory conditions. It has been observed that Shionone inhibits the expression of ECM1 and attenuates sepsis-induced injury in kidney and inflammatory factor levels in serum. In addition, Shionone may reduce inflammatory factor levels through the promotion of M2 macrophages by GM-CSF/STAT5/Arg1 pathway to alleviate sepsis induced inflammation in vitro.ConclusionThese findings demonstrate that Shionone can alleviate sepsis-induced AKI by promoting M2 macrophage polarization through regulating the ECM1/STAT5 pathway.https://www.frontiersin.org/articles/10.3389/fmed.2021.796743/fullacute kidney injuryECM1macrophagesinflammationshionone
spellingShingle Biao Zhang
Yi Xue
Jin Zhao
Huojun Jiang
Jiaoli Zhu
Hao Yin
Yizhen Qiu
Aihao Hu
Lingqi Xu
Yi Song
Xin Wang
Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
Frontiers in Medicine
acute kidney injury
ECM1
macrophages
inflammation
shionone
title Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
title_full Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
title_fullStr Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
title_full_unstemmed Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
title_short Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
title_sort shionone attenuates sepsis induced acute kidney injury by regulating macrophage polarization via the ecm1 stat5 pathway
topic acute kidney injury
ECM1
macrophages
inflammation
shionone
url https://www.frontiersin.org/articles/10.3389/fmed.2021.796743/full
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