JUN promotes hypertrophic skin scarring via CD36

Hypertrophic skin scarring following dermal injury causes extreme pain and psychological trauma for patients. Unfortuately, we do not have effective treatments to prevent or reverse skin scarring. Using RNA and ATAC sequencing of mouse and human fibroblasts, we show that JUN expressing fibroblasts are responsible for skin scarring by regulating CD36 expression. In summary, we show that CD36 antagonism by represent a therapeutic target to overcome JUN hypertrophic skin scarring. Overall design: RNA was obtained from FACS-isolated mouse fibroblast subpopulations (reticular and lipofibroblasts) from JUN+ and JUN- mice at post opeartive day 7 (POD), and human cultured JUN KO and JUN non-KO fibroblasts obtained from normal skin, scar, hypertrophic scar and keloid tissue. For mice samples, biological replicates were included; and for human cell samples technical replicates were included. To examine chromatin accessibility changes in response to JUN state in fibroblasts, an average of 50,000 cells were isolated per replicate by FACS in same fibroblasts types as above for both mouse and human samples. Biological replicates were included for mouse samples and technical replicates for human cell samples. To examine chromatin accessibility changes in response to JUN state in fibroblasts, an average of 50,000 cells were isolated per replicate by FACS in same fibroblasts types as above for both mouse and human samples. Biological replicates were included for mouse samples and technical replicates for human cell samples.