Bioinformatic analysis and experimental validation implicate STAT2-mediated angiogenic responses in rosacea pathogenesis.

Rosacea is a chronic skin condition characterized by facial erythema, flushing, and telangiectasia. Abnormalities in the vascular responses are associated with the development of rosacea. Our analysis of the GSE65914 dataset revealed differential expression of angiogenesis-related genes in rosacea lesions classified rosacea samples with distinct angiogenic molecular patterns. Further investigation of immune infiltration characteristics across angiogenic patterns identified unique immune signatures associated with VEGFAhigh MMP9low and VEGFAlow MMP9high subtypes. Moreover, STAT2 proteins were higher in the VEGFAhigh MMP9low pattern group. Increased expression of STAT2 was confirmed in rosacea patients and in the mice model of rosacea induced by LL37. Knockdown of STAT2 suppressed the tube formation ability of human umbilical vein endothelial cells, which implicated STAT2 participated in regulating angiogenic responses. In conclusion, our study characterized rosacea subtypes by distinct angiogenic molecular patterns and found that STAT2 may play a critical role in the regulation of angiogenic responses in rosacea. These insights may provide a promising target of rosacea therapies.