Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Pathology and Laboratory Medicine

Supervisor

Zheng, Xiufen

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.

Summary for Lay Audience

Sepsis is a life-threatening medical condition where the immune system overreacts to an infection and damages other organs. The majority of people who die from an infection develop sepsis, yet there is currently no reliable treatment to reduce the immune response in sepsis. Macrophages are a type of immune cell that can perform a variety of functions, from killing bacteria and viruses to cleaning up cellular debris and helping with tissue repair. They are first responders during an infection and release signals to other immune cells. Macrophage polarization is the term describing a macrophage’s choice to produce signals that increase or decrease the body’s immune response, which is important in the development of sepsis. Many biological signals in and around the macrophage can affect its polarization. Circular RNAs (circRNA) are a recently discovered type of molecule that can affect a cell’s function. CircRNAs differ from other RNAs by forming a closed loop, which make them last longer in the body to carry out their effects. We have previously found a circRNA called circRNA ASPH (circASPH), that is present in high amounts in the immune cells of sepsis patients. The role of circASPH in macrophage polarization has not been studied before. My research shows that circASPH can affect macrophage polarization. I found that macrophages with more circASPH released more inflammatory signals to promote a stronger immune response. This work will help identify potential new targets in immune cells to control their responses, which will help us develop more robust and specific treatments to combat sepsis.

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