The Mechanism of lncRNA NEAT1 in Alleviating Acute Respiratory Distress Syndrome Through miR-27b Regulated Nrf2 Pathway

June 16, 2021 updated by: Guangfa Zhu, Beijing Anzhen Hospital
The acute respiratory distress syndrome, formerly known as the acute lung injury (ARDS/ALI), is a critical illness with high mortality due to the lack of effective treatment. The pathogenesis of ARDS/ALI has not been fully elucidated. Nuclear factor E2-related factor 2 (Nrf2) plays a key role in regulating lung inflammation and oxidative stress which are closely related to lung injury in ARDS/ALI, but its regulatory mechanism remains unclear. The investigator's provious study shown that microRNA-27b (miR-27b) downregulated Nrf2 to aggravate lung inflammation and histological injury. Furthermore, in lipopolysaccharide (LPS)-induced cell (J774A.1) inflammation model, miR-27b was upregulated while the long non-coding RNA (lncRNA) NEAT1 was downregulated, the putative binding sites of lncRNA NEAT1 and miR-27b were successfully predicted by bioinformatics approach. Thus, the investigators propose that NEAT1 plays as a competing endogenous RNA (ceRNA) to adsorb miR-27b and liberate Nrf2, therefore, to attenuate lung inflammation and related lung injury in ARDS/ALI. This project aims to explore the role of the lncRNA NEAT1/ mir-27b /Nrf2 signal axis in the development and treatment of ARDS/ALI in patients, as well as in LPS-induced ALI animal and cell models by using bioinformatics, molecular biology, histomorphology and clinical phenotype approaches, and to clarify the new mechanism in ARDS/ALI development and to provide new therapeutic targets.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Collect blood and BALF from 400 ARDS patients at different time (at check-in, 24, 48 and 72 h after check-in the hospital) and 25 gender and age matching healthy controls. Use RT-PCR to detect the expression of lncRNA NEAT1、miR-27b and Nrf2 in blood and BALF of ARDS patients and health controls. The expressions of inflammatory and oxidative stress associated factors (NLRP3、NF-κB-P65、 p-P65、IκB、p-IκB、HO-1、NQO1、caspase-1、IL-1β、IL-6、IL-18、TNF-α) will be detected by western blot、ELISA and RT-PCR. Moreover, flow cytometry will be adopted to measure the numbers and kinds of cells in BALF. Then, analyze the differences of the expressions of lncRNA NEAT1、miR-27b and Nrf2 in the groups. To explore the correlation of expressions of lncRNA NEAT1、miR-27b and Nrf2 with inflammation and oxidative stress in the groups. Finally, to declare the relative of lncRNA NEAT1、miR-27b and Nrf2 with the time of mechanical ventilation, severity and mortality in 28 days of ARDS patients.

Study Type

Observational

Enrollment (Anticipated)

425

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100029
        • Department of Respiratory and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

We included ARDS patients from RICU、EICU、SICU、CCU in Beijing Anzhen hospital between 2020 and 2022

Description

Inclusion Criteria:

We included patients with acute respiratory distress according to 2012 ARDS Berlin new definition (Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA, 2012, 307(23):2526).

  • Acute or progressive dyspnea within 1 week with identify cause;
  • Chest radiograph/chest CT showed double lung infiltration, which could not be fully explained by pleural effusion, atelectasis, or nodules;
  • Respiratory failure cannot be fully explained by heart failure and fluid overload;
  • Hypoxemia, partial pressure of oxygen in arterial blood (PaO2)/oxygen fraction in air (FIO2) <150 mm Hg under PEEP ≥5 cm H2O, (mild ARDS: 200mmHg<PaO2/FiO2≤300mmHg, moderate ARDS: 100mmHg<PaO2/FiO2≤200mmHg, severe ARDS: PaO2/FiO2≤100mmHg);
  • 18~70 years old;
  • Agree to participate in the trial, and sign the informed consent.

Exclusion Criteria:

  • Age less than 18 years old;
  • Time of hospital stay <24 h;
  • Pregnancy;
  • Using V-V ECOM;
  • Cardiac index <1.5L·ml.min-1.m-2;
  • Pulmonary resection;
  • Pulmonary embolism ;
  • Refused to participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Control group
25 gender and age matching healthy controls
Other: no intervention
no intervention
ARDS group 1
100 ARDS patients at the time of check in hospital
Other: no intervention
no intervention
ARDS group 2
100 ARDS patients at the time of 24h after check in hospital
Other: no intervention
no intervention
ARDS group 3
100 ARDS patients at the time of 48h after check in hospital
Other: no intervention
no intervention
ARDS group 4
100 ARDS patients at the time of 72h after check in hospital
Other: no intervention
no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The expression of lncRNA NEAT1 in blood and BALF in all groups
Time Frame: up to 24 day
Use RT-PCR to measure the expression of lncRNA NEAT1 in blood and BALF in all groups
up to 24 day
The expression of miR-27b in blood and BALF in all groups
Time Frame: up to 3 day
Use RT-PCR to measure the expression of miR-27b in blood and BALF in all groups
up to 3 day
The expression of Nrf2 in blood and BALF in all groups
Time Frame: up to 3 day
Use RT-PCR and Wsetern blot to measure the expression of Nrf2 in blood and BALF in all groups
up to 3 day
The expression of inflammatory factors(IL-1β、IL-6、IL-18、TNF-α) in blood and BALF in all groups
Time Frame: up to 3 day
Use RT-PCR and ELISA to measure the expression of inflammatory factors(IL-1β、IL-6、IL-18、TNF-α) in blood and BALF in all groups
up to 3 day
The expression of oxidative stress associated factors in blood and BALF in all groups
Time Frame: up to 3 day
Use Western blot to measure the expression of oxidative stress associated factors(NLRP3、NF-κB-P65、 p-P65、IκB、p-IκB、HO-1、NQO1、caspase-1) in blood and BALF in all groups
up to 3 day
The numbers and kinds of inflammatory cells in BALF and blood in all groups
Time Frame: up to 3 day
Use flow cytometry to detect the number of inflammatory cells in BALF and blood in all groups
up to 3 day
The kinds of inflammatory cells in BALF and blood in all groups
Time Frame: up to 3 day
Use flow cytometry to detect the kinds of inflammatory cells(neutrophile、macrophage、 lymphocyte) in BALF and blood in all groups
up to 3 day
The time of mechanical ventilation of patients in ARDS groups
Time Frame: up to28 day
Record the time of mechanical ventilation of patients in ARDS groups
up to28 day
The severity of ARDS patients in ARDS groups
Time Frame: up to 28 day
Record the severity(PaO2/FiO2、OI、S/F、OSI) of ARDS patients in ARDS groups
up to 28 day
the mortality in 28 days of ARDS patients
Time Frame: up to 28 day
Record the mortality in 28 days of ARDS patients
up to 28 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The differences and correlation of the expressions of lncRNA NEAT1、miR-27b and Nrf2 in the groups
Time Frame: up to 28 day
Analyse the differences of the expressions of lncRNA NEAT1、miR-27b and Nrf2 in the groups, and to explore the relations between the three(lncRNA NEAT1、miR-27b and Nrf2) in different groups.
up to 28 day
The correlation of expressions of lncRNA NEAT1、miR-27b and Nrf2 with inflammation and oxidative stress in the groups.
Time Frame: up to 28 day
To explore the correlation of expressions of lncRNA NEAT1、miR-27b and Nrf2 with inflammation and oxidative stress in the groups.
up to 28 day
The relative of lncRNA NEAT1、miR-27b and Nrf2 with the time of mechanical ventilation, severity and mortality in 28 days of ARDS patients
Time Frame: up to 28 day
To declare the relative of lncRNA NEAT1、miR-27b and Nrf2 with the time of mechanical ventilation, severity and mortality in 28 days of ARDS patients
up to 28 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Anzhen Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2021

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

January 11, 2020

First Submitted That Met QC Criteria

June 16, 2021

First Posted (Actual)

June 24, 2021

Study Record Updates

Last Update Posted (Actual)

June 24, 2021

Last Update Submitted That Met QC Criteria

June 16, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 81970067

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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