miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function

Background. Recent literature has reported the use of circulating microRNAs (miRNAs) as biomarkers for sepsis. Immune cells play an essential role in the pathophysiology of sepsis. The aim of this prospective study was to identify miRNAs in peripheral blood mononuclear cells (PBMC) that could differ...

Full description

Saved in:
Bibliographic Details
Main Authors: Guoping Zheng, Guanguan Qiu, Menghua Ge, Jianbiao Meng, Geng Zhang, Jiangmei Wang, Ruoqiong Huang, Qiang Shu, Jianguo Xu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2020/4370983
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832550979623452672
author Guoping Zheng
Guanguan Qiu
Menghua Ge
Jianbiao Meng
Geng Zhang
Jiangmei Wang
Ruoqiong Huang
Qiang Shu
Jianguo Xu
author_facet Guoping Zheng
Guanguan Qiu
Menghua Ge
Jianbiao Meng
Geng Zhang
Jiangmei Wang
Ruoqiong Huang
Qiang Shu
Jianguo Xu
author_sort Guoping Zheng
collection DOAJ
description Background. Recent literature has reported the use of circulating microRNAs (miRNAs) as biomarkers for sepsis. Immune cells play an essential role in the pathophysiology of sepsis. The aim of this prospective study was to identify miRNAs in peripheral blood mononuclear cells (PBMC) that could differentiate between sepsis and infection based on Sepsis-3 definition. Methods. A total of 62 patients (41 with sepsis and 21 with infection suffering from pneumonia but without sepsis) and 20 healthy controls were enrolled into the study. PBMC at admission were examined for a panel of 4 miRNAs (miR-10a, miR-17, miR-27a, and miR-125b), which have been documented to participate in inflammatory response in immune cells, via qRT-PCR. Data were validated in a mouse model of sepsis induced via cecal ligation and puncture (CLP) and THP-1 monocytes. Results. miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with patients with infection and healthy controls. miR-10a levels were negatively correlated with disease severity scores as well as levels for c-reactive protein and procalcitonin. In addition, low miR-10a expression had a diagnostic value for sepsis and a prognostic value for 28-day mortality in receiving operating characteristic analysis. Compared with infection patients and healthy controls, PBMC from sepsis patients also had higher levels of mitogen-activated kinase kinase kinase 7 (MAP3K7), a known target protein of miR-10a and an activator of the NF-κB pathway. In the mouse model of CLP-induced sepsis, miR-10a levels in PBMC were significantly decreased as early as 8 h after CLP. Overexpression of miR-10a in THP-1 cells significantly reduced the expression of MAP3K7 and proinflammatory cytokines including IL-6, TNF-α, and MCP-1. Conclusions. PBMC miR-10a levels are decreased in sepsis and negatively correlated with the disease severity. Levels of miR-10a could distinguish between sepsis and infection and predict 28-day mortality. miR-10a plays an anti-inflammatory role in the pathogenesis of sepsis.
format Article
id doaj-art-6e8c91e3ddc14abfb8f295d7b82dff2a
institution Kabale University
issn 0962-9351
1466-1861
language English
publishDate 2020-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-6e8c91e3ddc14abfb8f295d7b82dff2a2025-02-03T06:05:15ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/43709834370983miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory FunctionGuoping Zheng0Guanguan Qiu1Menghua Ge2Jianbiao Meng3Geng Zhang4Jiangmei Wang5Ruoqiong Huang6Qiang Shu7Jianguo Xu8Shaoxing Second Hospital, 123 Yanan Road, Shaoxing, Zhejiang 312000, ChinaShaoxing Second Hospital, 123 Yanan Road, Shaoxing, Zhejiang 312000, ChinaShaoxing Second Hospital, 123 Yanan Road, Shaoxing, Zhejiang 312000, ChinaTongde Hospital of Zhejiang, 132 Tianmushan Road, Hangzhou, Zhejiang 310007, ChinaTongde Hospital of Zhejiang, 132 Tianmushan Road, Hangzhou, Zhejiang 310007, ChinaChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, Zhejiang 310052, ChinaChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, Zhejiang 310052, ChinaChildren’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Road, Hangzhou, Zhejiang 310052, ChinaShaoxing Second Hospital, 123 Yanan Road, Shaoxing, Zhejiang 312000, ChinaBackground. Recent literature has reported the use of circulating microRNAs (miRNAs) as biomarkers for sepsis. Immune cells play an essential role in the pathophysiology of sepsis. The aim of this prospective study was to identify miRNAs in peripheral blood mononuclear cells (PBMC) that could differentiate between sepsis and infection based on Sepsis-3 definition. Methods. A total of 62 patients (41 with sepsis and 21 with infection suffering from pneumonia but without sepsis) and 20 healthy controls were enrolled into the study. PBMC at admission were examined for a panel of 4 miRNAs (miR-10a, miR-17, miR-27a, and miR-125b), which have been documented to participate in inflammatory response in immune cells, via qRT-PCR. Data were validated in a mouse model of sepsis induced via cecal ligation and puncture (CLP) and THP-1 monocytes. Results. miR-10a levels in PBMC at admission were significantly lower in sepsis patients compared with patients with infection and healthy controls. miR-10a levels were negatively correlated with disease severity scores as well as levels for c-reactive protein and procalcitonin. In addition, low miR-10a expression had a diagnostic value for sepsis and a prognostic value for 28-day mortality in receiving operating characteristic analysis. Compared with infection patients and healthy controls, PBMC from sepsis patients also had higher levels of mitogen-activated kinase kinase kinase 7 (MAP3K7), a known target protein of miR-10a and an activator of the NF-κB pathway. In the mouse model of CLP-induced sepsis, miR-10a levels in PBMC were significantly decreased as early as 8 h after CLP. Overexpression of miR-10a in THP-1 cells significantly reduced the expression of MAP3K7 and proinflammatory cytokines including IL-6, TNF-α, and MCP-1. Conclusions. PBMC miR-10a levels are decreased in sepsis and negatively correlated with the disease severity. Levels of miR-10a could distinguish between sepsis and infection and predict 28-day mortality. miR-10a plays an anti-inflammatory role in the pathogenesis of sepsis.http://dx.doi.org/10.1155/2020/4370983
spellingShingle Guoping Zheng
Guanguan Qiu
Menghua Ge
Jianbiao Meng
Geng Zhang
Jiangmei Wang
Ruoqiong Huang
Qiang Shu
Jianguo Xu
miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function
Mediators of Inflammation
title miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function
title_full miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function
title_fullStr miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function
title_full_unstemmed miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function
title_short miR-10a in Peripheral Blood Mononuclear Cells Is a Biomarker for Sepsis and Has Anti-Inflammatory Function
title_sort mir 10a in peripheral blood mononuclear cells is a biomarker for sepsis and has anti inflammatory function
url http://dx.doi.org/10.1155/2020/4370983
work_keys_str_mv AT guopingzheng mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT guanguanqiu mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT menghuage mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT jianbiaomeng mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT gengzhang mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT jiangmeiwang mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT ruoqionghuang mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT qiangshu mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction
AT jianguoxu mir10ainperipheralbloodmononuclearcellsisabiomarkerforsepsisandhasantiinflammatoryfunction