Role of endothelial microRNA 155 on capillary leakage in systemic inflammation
نویسندگان
چکیده
Abstract Background Capillary leakage is a key contributor to the pathological host response infections. The underlying mechanisms remain incompletely understood, and role of microRNAs (MIR) has not been investigated in detail. We hypothesized that specific MIRs might be regulated directly endothelium thereby contributing vascular leakage. Methods SmallRNA sequencing endotoxemic murine pulmonary endothelial cells (ECs) was done detect MIRs. In vivo models: transgenic zebrafish (flk1:mCherry/l-fabp:eGFP-DPB), knockout/wildtype mouse (B6.Cg-Mir155tm1.1Rsky/J); disease LPS 17.5 mg/kgBW cecal ligation puncture (CLP); vitro stimulated human umbilical vein EC (HUVECs), transendothelial electrical resistance. Results Endothelial MIR155 identified as promising candidate ECs (25 × upregulation). Experimental overexpression line HUVECs sufficient induce spontaneous To contrary, genetic reduction protects against permeability both endotoxemia heterozygote knockout mice improving survival by 40%. A tight junction protein, Claudin-1, down-regulated experimental overexpression. Translationally, detectable at high levels bronchoalveolar fluid patients with ARDS compared healthy subjects. Conclusions found upregulated men part systemic inflammatory contribute pathophysiology Claudin-1-dependent manner. Future studies have clarify whether could potential therapeutic target.
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ژورنال
عنوان ژورنال: Critical Care
سال: 2021
ISSN: ['1364-8535', '1466-609X']
DOI: https://doi.org/10.1186/s13054-021-03500-0