Abstract
Background
Angiogenesis is both a notable characteristic of psoriasis and a key driver of its pathogenesis. Calcipotriol has been used for the treatment of psoriasis for several decades, yet few studies have focused on its microvascular mechanism utilizing appropriate animal models. The K14 vascular endothelial growth factor (VEGF) transgenic mouse model is an ideal animal model to study the microvascular mechanism of psoriasis.
Objectives
To explore the mechanism through which calcipotriol exerts its anti-angiogenic effect in psoriasis using the K14 VEGF transgenic mouse model
Materials & Methods
Having established the transgenic mouse model, the K14 VEGF mice were randomly divided into three groups with topical treatment with either vehicle cream, calcipotriol ointment or halometasone cream. The skin of the mice was subsequently collected to evaluate the level of VEGF and pigment epithelium-derived factor (PEDF) as well as microvascular density (MVD). Furthermore, the phosphorylation level of JAK/STAT3 was also investigated.
Results
In contrast to C57 mice, there was an observed increment in the level of VEGF and MVD in the skin of K14 VEGF mice, while the PEDF level was decreased. Moreover, we found that topical calcipotriol treatment affected the ratio of VEGF to PEDF, and decreased MVD in the skin of K14 VEGF mice. In addition, calcipotriol also up-regulated vitamin D receptor and inhibited the JAK/STAT3 signalling pathway
Conclusion
Calcipotriol inhibits psoriasis-like angiogenic features by suppressing VEGF, increasing PEDF and ultimately decreasing MVD in the skin of K14 VEGF mice, possibly involving the JAK/STAT3 pathway.
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Acknowledgments
this work was financially supported by the Dermatology Research Fund of China Association of Integrative Medicine (No.2018-2).
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Cao, M., Mei, L., Xiao, M. et al. Calcipotriol inhibits psoriasis-like angiogenic features in K14-VEGF transgenic mice. Eur J Dermatol 32, 24–33 (2022). https://doi.org/10.1684/ejd.2022.4230
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DOI: https://doi.org/10.1684/ejd.2022.4230