The role of Angiopoietin-like protein 4 in macrophage activation

• Main Author: Wee, Jonathan Wei Kiat
• Other Authors: Tan Nguan Soon
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2021
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/151419
• Institution: Nanyang Technological University

Angiopoietin-like protein 4 (Angptl4) is a matricellular protein that associates with extracellular matrix proteins, mediating complex cell-cell, and cell-matrix interactions. It has been implicated in various inflammation-associated diseases, including atherosclerosis, pulmonary damage, and wound healing. Studies have shown Angptl4 to be a key regulator of wound healing, affecting different processes like cell adhesion, migration, and angiogenesis. However, very few reports describe a direct role for Angptl4 in immune cell development and response. Using single-cell RNA sequencing to examine the temporal changes in the immune cell landscape of excisional wounds from wild type and Angplt4-knockout (Angplt4-/-) mice revealed that Angptl4-/- wounds had a stalled inflammatory phase. We identified interferon activated protein 202B (ifi202b) to be consistently upregulated in Angptl4-/- macrophages. We confirmed that ifb202b significantly impacted multiple gene networks involved in the cell fate of monocytes and the functions of monocyte-derived macrophages. Taken altogether, we show the importance of Angptl4 in macrophage function during wound healing and its parallels to diabetic wounds during deficiency.