ETV2 Dysregulation in Scleroderma Endothelial Cells
Abstract
This proposal addresses the Focus Area, Define functional role of epigenetic changes, multiple cell types, and molecules that mediate pathogenesis and/or initiate or propagate organ-specific disease activity using preclinical models and clinical samples. Scleroderma is a debilitating autoimmune disease characterized by inflammation, scarring of the tissues including the skin, and decrease in blood vessel formation throughout the body, all of which trigger potentially lethal damage to the organs. In particular, most patients experience vascular abnormalities as one of their first symptoms, which trigger tissue stiffness and related complications later on in the course of the disease. In this proposal, we plan to determine the cause for vascular abnormalities in scleroderma. By using next-generation sequencing techniques to scan the genes in patient-derived vascular cells, we identified increased DNA binding of ETV2, which is a transcription factor that governs gene expression, in scleroderma vascular cells. We also found that the expression of ETV2 was increased in these cells, and manipulation of ETV2 expression alters the functions of the vascular cells. In this study, we plan to determine ETV2-target genes in scleroderma vascular cells, and further investigate the roles of selected ETV2- target genes in these cells. We hypothesize that dysregulation of ETV2 and its target genes play critical roles in vascular dysfunction in scleroderma. This project is innovative in its concept, since ETV2 and its target genes have not been examined in scleroderma vasculature before. It is also innovative in using vascular cells isolated from patient biopsies, coupled with state-of-the-art methodologies and integrative analytical approaches to identify novel ETV2 targets. Our data will demonstrate a critical role of ETV2 in endothelial function, and provide novel therapeutic targets for this disease, and specifically benefit patients with vascular complications.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210360
Entities
People
- Pei-suen Tsou
Organizations
- United States Army
- University of Michigan