Related Experiment Video
Updated: Nov 16, 2025
Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Role of endothelial microRNA 155 on capillary leakage in systemic inflammation
Valerie Etzrodt1, Temitayo O Idowu1, Heiko Schenk1,2
1Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
Background:
Capillary leakage is a key contributor to the pathological host response to infections. The underlying mechanisms remain incompletely understood, and the role of microRNAs (MIR) has not been investigated in detail. We hypothesized that specific MIRs might be regulated directly in the endothelium thereby contributing to vascular leakage.
Methods:
SmallRNA sequencing of endotoxemic murine pulmonary endothelial cells (ECs) was done to detect regulated vascular MIRs. In vivo models: transgenic zebrafish (flk1:mCherry/l-fabp:eGFP-DPB), knockout/wildtype mouse (B6.Cg-Mir155tm1.1Rsky/J); disease models: LPS 17.5 mg/kgBW and cecal ligation and puncture (CLP); in vitro models: stimulated human umbilical vein EC (HUVECs), transendothelial electrical resistance.
Results:
Endothelial MIR155 was identified as a promising candidate in endotoxemic murine pulmonary ECs (25 × upregulation). Experimental overexpression in a transgenic zebrafish line and in HUVECs was sufficient to induce spontaneous vascular leakage. To the contrary, genetic MIR155 reduction protects against permeability both in vitro and in endotoxemia in vivo in MIR155 heterozygote knockout mice thereby improving survival by 40%. A tight junction protein, Claudin-1, was down-regulated both in endotoxemia and by experimental MIR155 overexpression. Translationally, MIR155 was detectable at high levels in bronchoalveolar fluid of patients with ARDS compared to healthy human subjects.
Conclusions:
We found that MIR155 is upregulated in the endothelium in mouse and men as part of a systemic inflammatory response and might contribute to the pathophysiology of vascular leakage in a Claudin-1-dependent manner. Future studies have to clarify whether MIR155 could be a potential therapeutic target.
Insights
MicroRNA 155 (MIR155) is upregulated in endothelial cells during infection, causing vascular leakage by downregulating Claudin-1. Reducing MIR155 protects against this leakage and improves survival in disease models.
Area of Science:
- Vascular Biology
- Molecular Medicine
- MicroRNA Research
Background:
- Capillary leakage is a critical factor in infection pathology.
- Mechanisms of vascular leakage are not fully understood.
- The role of microRNAs (MIRs) in endothelial regulation is largely unexplored.
Purpose of the Study:
- To investigate the role of specific microRNAs (MIRs) in endothelial cells during infection.
- To test the hypothesis that MIRs are regulated in endothelium and contribute to vascular leakage.
Main Methods:
- Small RNA sequencing of endotoxemic murine pulmonary endothelial cells (ECs).
- In vivo models (zebrafish, mice), disease models (LPS, CLP), and in vitro models (HUVECs, transendothelial electrical resistance).
Main Results:
- MicroRNA 155 (MIR155) was significantly upregulated in endotoxemic murine pulmonary ECs.
- MIR155 overexpression induced vascular leakage in zebrafish and HUVECs.
- Genetic reduction of MIR155 protected against vascular permeability and improved survival in mice.
- Claudin-1 was downregulated by MIR155, linking it to vascular leakage.
- MIR155 was elevated in bronchoalveolar fluid of ARDS patients.
Conclusions:
- MIR155 is upregulated in the endothelium during systemic inflammation in mice and humans.
- MIR155 contributes to vascular leakage pathophysiology via Claudin-1.
- MIR155 represents a potential therapeutic target for vascular leakage.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:38Inflammation