The treatment of rosacea has been

The treatment of rosacea has been a big challenge for both patients and clinicians, mainly due to the lack of approaches targeting pathogenic pathway. Although the pathogenesis of rosacea is unknown, a line of evidence suggests that dihydroergotamine the development of rosacea is driven by a defective permeability barrier. In addition to the induction of pre-inflammatory cytokine releases, barrier disruption increases the epidermal SP activity and LL-37 expression. Epidermal proteases, including kallikrein-related peptidases 5 and 7 (KLK5, KLK7), degrade LL-37 to different active fragments of LL-37, including FA-29. The active forms of LL-37 cause erythema and vasodilatation, as well as cytokine release. Moreover, LL-37 upregulates vascular endothelial growth factor expression. However, activation of PAR-2 by SP also undermined the permeability barrier. The latter could exacerbate rosacea. The clinical evidence that improvement of permeability barrier alone benefits rosacea also supports the pathogenic role of the permeability barrier in rosacea. The putative pathogenic role of the permeability barrier in rosacea and the mechanisms by which tranexamic acid benefits rosacea are illustrated in Figure 6.
Acknowledgments This project was supported by the National Natural Science Fund (81201217) and the Beijing Natural Science Fund (7122181).