The Endothelial Cell Response to Inflammation, the Functional Role of the Endothelial-enriched Protein KANK3 and the Adipose Tissue Transcriptome

Abstract

<p>A compilation of three complementary projects explores various facets of endothelial cell biology and transcriptomics, illuminating the intricate dynamics underlying cellular responses to specific stimuli across different tissues. <p>The first project examines how endothelial cells react to the inflammatory molecule tumour necrosis factor (TNF), by studying these cells over time after TNF exposure. We identified distinct gene expression patterns and revealed two central temporal phases of gene upregulation in the endothelial response. The induction of interferon response genes, without de novo interferon production, was further investigated. An online resource was developed for comprehensive data exploration (<a href=https://www.endothelial-response.org>www.endothelial-response.org</a>). <p>The second project analysed adipose tissue to define cell type enriched transcripts and differences between the sexes and depot types. We found mesothelial cells to be the main driver for heterogeneity between subcutaneous and visceral adipose tissue. This data is accessible through the Human Protein Atlas. <p>The third project focuses on KANK3, which was predicted to be an endothelial enriched gene in the previous study, and others from the group. Our findings show that KANK3 is endothelial specific in multiple tissues through the body, inhibition of KANK3 in endothelial cells affects cell motility, expression of blood clotting proteins on gene and protein level, and thrombin generation. <p>Together, these projects enhance our understanding of endothelial cell responses to inflammation and detail the functional investigation of an uncharacterised endothelial protein. Each project offers a different perspective, by examining temporal responses, functional changes, and tissue-wide patterns. This multifaceted approach deepens our insights into cell biology and furthers our understanding of critical health processes.