PDGF promotes skin fibrosis via a novel mechanism mediated by signaling through MCHR1

We identified several differentially expressed genes in dermal fibroblasts from patients with SSc compared to their healthy twins, including the upregulation of MCHR1 in SSc fibroblasts. We also uncovered MCHR1 as a hub gene with the highest centrality degree in the network analysis, suggesting important biological role. We identified PDGF as the pro-fibrotic growth factor that increases MCHR1 levels. We further determine that PDGF induction of dermal fibroblast activation and pro-fibrotic factor production is mediating by MCHR1 using silencing and chemical inhibition of MCHR1. Overall design: Compare the expression profiling of primary human skin fibroblasts from healthy donors transfected with siRNA to silence MCHR1 with PDGFBB or vehicle treatment