MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• ADAM15 (a disintegrin and metalloproteinase 15) is upregulated during inflammation and sepsis, contributing to endothelial hyperpermeability.
• ADAM15's diverse functional domains make it a potential therapeutic target for various diseases.

Purpose of the Study:

• To investigate if microRNAs targeting ADAM15 can modulate ADAM15-induced endothelial barrier dysfunction during septic conditions.
• To identify specific microRNAs capable of altering ADAM15 expression and its functional consequences.

Main Methods:

• In silico analysis and luciferase reporter assays were used to identify ADAM15-targeting microRNAs in human vascular endothelial cells.
• Transfection with miR-147b mimics and antagomirs was performed to assess effects on ADAM15 expression.
• Endothelial barrier function was evaluated by measuring transendothelial electric resistance and albumin flux.

Main Results:

• miR-147b was identified as a microRNA targeting the 3' UTR of ADAM15.
• miR-147b mimic transfection decreased ADAM15 expression, while antagomir increased it.
• miR-147b mimics attenuated lipopolysaccharide (LPS)-induced endothelial barrier dysfunction, whereas antagomirs exacerbated it.

Conclusions:

• miR-147b plays a role in regulating endothelial barrier function by targeting ADAM15 expression.
• These findings suggest miR-147b as a potential therapeutic tool for managing sepsis-related endothelial dysfunction.