Electronic Thesis and Dissertation Repository

Role of Circular RNA ASPH in Macrophage Polarization and Response in Sepsis

Tan Ze Wang, Western University

Abstract

Circular RNAs (circRNAs), a novel non-coding RNA species generated by back-splicing, has been shown to participate in gene regulation of leukocytes. Our previous RNA sequencing results show circular RNA ASPH (circASPH) to be highly expressed in peripheral blood mononuclear cells of sepsis patients at the start of intensive care. Macrophages, as ubiquitous innate immune cells, are responsible for the recruitment of other immune cells at sepsis onset. This work investigates the role of circASPH in the regulation of macrophage polarization in sepsis. Using an in vitro THP-1 cell model, it was found that circASPH levels peaked after 24 h of M1 polarization and after 12 h of M2 polarization. Knockdown of circASPH prior to polarization resulted in downregulation of M1 gene expression and cytokine secretion. These results suggest a proinflammatory role of circASPH in macrophage polarization and support its potential as a novel biomarker or therapeutic target for sepsis.