Deletion of adipocyte Sine Oculis Homeobox Homolog 1 prevents lipolysis and attenuates skin fibrosis

The study investigates the role of sine oculis homeobox homolog 1 (SIX1) in dermal fibrosis associated with systemic sclerosis (SSc). Elevated SIX1 expression was found in SSc skin samples and correlated with adipose-associated genes. Localization studies showed increased SIX1 signals in dermal white adipose tissue (DWAT) in SSc and experimental models. Deleting SIX1 globally and specifically in adipocytes reduced fibrotic gene expression and dermal adipocyte shrinkage caused by bleomycin treatment. The study also found a link between elevated SIX1 and increased expression of pro-fibrotic mediators SERPINE1 and PAI-1. However, SIX1 deletion did not affect cellular trans differentiation. These findings suggest that SIX1 could be a potential target for treating dermal fibrosis in SSc.