ADAR1 is targeted by miR-143 to regulate IL-1β-induced endothelial activation through the NFκB pathway

The International Journal of Biochemistry & Cell Biology
Yuanzhuo ChenYugang Zhuang

Abstract

Excessive endothelial activation by inflammatory mediators is a critical contributing factor of sepsis pathophysiology. ADAR1 (adenosine deaminase acting on RNA), an enzyme that binds and edits double-stranded RNAs, exhibits immune regulatory properties. Whether ADAR1 is involved in the pathophysiology of sepsis is unclear. In the present study, we used human umbilical endothelial cells (HUVECs) as an in vitro model system to investigate the roles of ADAR1 in interleukin (IL)-1β-induced endothelial activation. We found that stimulation with IL-1β caused opposite changes in the expression of ADAR1 and the adherence molecules VCAM-1 and ICAM-1. ADAR1 overexpression reduced while ADAR1 knockdown enhanced IL-1β-induced HUVEC activation as assessed by ICAM-1 and VCAM-1 expression and THP-1 monocyte recruitment. Furthermore, ADAR1 was confirmed to be a direct target of miR-143 in HUVECs by a luciferase reporter assay, and miR-143 overexpression promoted while miR-143 knockdown inhibited HUVEC activation by IL-1β. In addition, ADAR1 overexpression prevented the enhancement effects of miR-143 overexpression on IL-1β-induced HUVEC activation. Our mechanistic studies revealed that ADAR1 overexpression reduced while ADAR1 knockdown enhanc...Continue Reading

References

Nov 19, 2015·RNA·Manolis MaragkakisZissimos Mourelatos

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.