The Effect and Mechanism of lncRNA NBR2 Regulating Endothelial Pyroptosis by Targeting GSDMD in Sepsis

Zhongda Hospital, School of Medicine, Southeast University

Sepsis is a life-threatening disease characterized by multi-organ failure due to dysregulated host response to infection, with high global mortality of 30-50%. One of the most important pathophysiologic hallmarks in sepsis is vascular endothelial injury that contributes to the severity and outcome of the syndrome. Effective treatments for endothelial cell injury in sepsis have been lacking to improve prognosis. Endothelial pyroptosis is a vital mechanism of vascular endothelial injury in sepsis; mitigation or abolishment of endothelial cell pyroptosis alleviate vascular endothelial damage and improve the prognosis of sepsis mice. Gasdermin D (GSDMD) mediated endothelial pyroptosis plays a critical role in modulating vascular endothelial injury in sepsis.

Long non-coding RNA (lncRNA), as a class of non-coding protein RNA longer than 200 kD, contributes to a variety of cell biological processes. The dysregulation of lncRNA results in the occurrence and development of tumors, diabetes, sepsis and other diseases. Therefore, we detected lncRNA and mRNA expression profile in 26 blood samples of septic patients using Arraystar LncRNA Microarray. We found lncRNA NBR2 regulates septic endothelial pyroptosis.

To assess any correlation of pyroptosis levels with relevant endothelial cell injury parameters and determine the prognostic value in septic patients. we measured the levels of pyroptosis in patients admitted to the Department of Critical Care Medicine for sepsis and investigated the correlation with related markers of endothelium injury. Furthermore, we determined the prognostic value of pyroptosis levels for the mortality of patients with sepsis.

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Other: the levels of pyroptosis

Detailed Description

We measured the levels of pyroptosis in patients admitted to the Department of Critical Care Medicine for sepsis and investigated the correlation with related markers of endothelium injury. Furthermore, we determined the prognostic value of pyroptosis levels for the mortality of patients with sepsis.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Fei Peng, Dr; Phone Number: 025-83262553; Email: afei0312@163.com
• Study Contact Backup: Name: Yi Yang, Prof.; Phone Number: 025-83262553; Email: yiyiyang2004@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Zhongda Hospital, School of Medicine, Southeast University
      • Contact: Fei Peng, Dr; Phone Number: 025-83262553; Email: afei0312@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

sepsis was defined according to "sepsis 3.0", which including suspected or confirmed infection and increased SOFA ≥ 2, confirmed by two experienced intensive care physicians. The infection was defined on the basis of infection sites, clinical features, clinical microbiology, and imaging tests. Septic shock was defined as a vasopressor requirement to maintain a mean arterial pressure of 65 mmHg or greater and serum lactate level greater than 2 mmol/L in the absence of hypovolemia.

Description

Inclusion Criteria:

• Suspected or confirmed infection
• The sequential organ failure score (SOFA score) increases by more than or equal to 2 points on the basis
• Sign the informed consent

Exclusion Criteria:

1. the age < 18 or > 80 years of age
2. pregnant
3. tumor
4. viral hepatitis or liver cirrhosis
5. chronic renal tubular nephritis, chronic renal insufficiency
6. ulcerative colitis or crohn's disease
7. active systemic lupus erythematosus (SLE)
8. acute myocardial infarction
9. acute pancreatitis
10. engaged in other clinical subjects

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
survivors; Improve or under treatment	Other: the levels of pyroptosis; Blood samples were taken to detect plasma lncRNA NBR2 levels and GSDMD protein level.
nonsurvivors; all-cause 28-day mortality	Other: the levels of pyroptosis; Blood samples were taken to detect plasma lncRNA NBR2 levels and GSDMD protein level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	all-cause 28-day mortality	28-day

Collaborators and Investigators

• Sponsor: Jianfeng Xie

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: endothelial cell injury; pyroptosis; lncRNA NBR2; gasdermin D
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis
• Other Study ID Numbers: SoutheastUChina

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No