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- Academic Editors
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†These authors contributed equally.
Background: Current studies have demonstrated that disintegrin and
metalloproteinase 17 (ADAM17) plays a critical role in the pathogenesis of
sepsis. MicroRNA (miR)-145 is known to control immune responses as an
anti-inflammatory modulatory molecule. However, a fundamental understanding of
how miR-145 regulates ADAM17 and, more broadly, sepsis-induced inflammatory
response remains unknown. Methods: We used western blotting and
quantitative real-time PCR (qRT-PCR) to measure expression levels of ADAM17 and
miR-145. Enzyme-linked immunosorbent assays (ELISA) were performed to measure
cytokine production. To determine if ADAM17 is a target gene of miR-145,
bioinformatics analyses and luciferase reporter assays were conducted. The
impacts of ADAM17 and miR-145 on sepsis-induced inflammatory responses were
accessed in vitro using human umbilical endothelial cells (HUVECs)
treated with lipopolysaccharide (LPS). Sepsis-induced inflammatory response was
measured in vivo using a polymicrobial septic mouse model induced by
cecal ligation and puncture (CLP) with pre-injection of a miR-145 agomir.
Results: In HUVECs treated with LPS, miR-145 expression was
downregulated and miR-145 negatively regulated ADAM17 expression through direct
binding to the ADAM17 transcript 3