RUNX1 is Expressed in a Subpopulation of Dermal Fibroblasts and Higher RUNX1 Levels are Associated with the Severity of Systemic Sclerosis

Abstract

The activation of Runt-related transcription factor 1 (RUNX1) in fibroblasts has been implicated in wound healing and fibrosis; however, the role of RUNX1 in the fibrotic progression of the autoimmune disease systemic sclerosis (SSc) is not known. Through gene expression analysis, we have demonstrated an association between the severity of dermal fibrosis and the expression levels ofRUNX1in the skin of patients with SSc. Additionally, we identified hypomethylated CpG sites proximal to theRUNX1gene, implicating their potential role in the increased expression ofRUNX1. Analysis of single-cell RNA-seq data from skin biopsies of individuals with SSc revealed thatRUNX1is higher in subpopulations of fibroblasts enriched in SSc, which are believed to contribute to fibrosis. Lastly, modulation ofRUNX1activity using an inhibitor caused a reduction in fibroblast contraction and proliferation rates. Altogether, this study is the first to demonstrate a potential role forRUNX1in the pathogenesis of systemic sclerosis dermal fibrosis.