YKL-40 Enhanced the Permeability of HDMECs with Histamine Through Activating Akt and p38 Pathways

Abstract Background, YKL-40 is currently considered as an important marker of endothelial dysfunction. Chronic spontaneous urticaria (CSU) is a common vascular skin disease. The increased vascular permeability play an important role in the occurrence and pathogenesis of CSU.Objective, the aim of this study is to explore the role of YKL-40 on the permeability of HDMECs.Methods, in this study, the mRNA level of YKL-40 in human mast cell line (HMC-1) were detected by RT-PCR. The effects of YKL-40 on vascular permeability, VE-cadherin release, VE-cadherin disruption in human dermal microvascular endothelial cells (HDMECs) were investigated by transwell, ELISA or immunofluorescence. The phosphorylation of VE-cadherin, p38 and Akt, in histamine plus YKL-40 treated HDMECs were detected by Western Blot.Results, we found that YKL-40 significantly promoted the permeability changes and leaded to the released, disruption of VE-cadherin in HDMECs induced by histamine. Furthermore, YKL-40 also enhanced the Akt and p38 pathways. Conclusion, we suggest that YKL-40 may serve as pro-permeability cytokines, and play a role in the pathogenesis of CSU. This study will help to further elucidate the pathogenesis of CSU and provide a new target for the development of anti-histamine resistance drugs for CSU.