1327 Effect of ginsenoside Rd on dermal epidermal junction in fibroblast

Abstract

Frontal fibrosing alopecia (FFA) is a devastating, progressive scarring alopecia with increasing worldwide prevalence. Its pathogenesis is unknown, leading to lack of targeted therapeutics. We sought to elucidate the molecular profile of lesional and non-lesional scalp from patients with FFA (n¼12) as compared with alopecia areata (AA) (n¼10) and healthy control scalp (n¼3). Overall, FFA tissues showed higher induction of key T H 1 (IFN-g, CXCL9, CXCL10; p<0.05), and JAK-STAT signaling and T-cell activation mediators (JAK3, STAT1, IL-2RA; p<0.05), in FFA lesional, but also in non-lesional scalp, compared with controls and AA tissues. Several T H 2/T H 9 markers, such as IL-10 (p<0.01), CCL13 (p<0.01), IL-13, and IL-9 were also upregulated in FFA lesions. The T H 17/T H 22-regulated marker S100A7 was upregulated in FFA lesions (p<0.01), and its expression also significantly correlated with clinical severity (as measured by FFA Severity Index [FFASI]) in patients with more severe disease (p<0.05). Hair keratins did not show decreased expression in FFA, unlike in AA in which these genes (KRTAP1, KRT40, KRT75, KRT83, KRT84, KRT86) showed characteristically significant suppressions versus control scalp (p<0.05). This is the first study to characterize the molecular fingerprinting of FFA tissues. Our data suggests that FFA is a highly inflammatory disease already at the non-lesional state, with predominant T H 1 and JAK-STAT pathway involvement without inhibition of hair keratins, the hallmark of AA. These findings identify JAK-STAT signaling as a potential therapeutic target for this debilitating disease.