Vitamin D suppress the production of vascular endothelial growth factor in mast cell by inhibiting PI3K/Akt/p38 MAPK/HIF-1α pathway in chronic spontaneous urticaria

• Published in: Clinical immunology (Orlando, Fla.) Vol. 215; p. 108444
• Main Authors: Zhao, Jun-Wei, Ping, Jie-Dan, Wang, Yong-Feng, Liu, Xia-Nan, Li, Nan, Hu, Zhong-Lan, Ming, Liang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2020
• Subjects: Adult; Chronic spontaneous urticaria; Chronic Urticaria - drug therapy; Chronic Urticaria - metabolism; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunoglobulin E - metabolism; Male; Mast cell; Mast Cells - drug effects; Mast Cells - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Vascular endothelial growth factor; Vascular Endothelial Growth Factors - metabolism; Vitamin D; Vitamin D - pharmacology; CSU; VDR; IgE; VEGF; Chronic spontaneous urticaria; HIF-1α; LC-MS/MS; Vitamin D; VDBP; iTRAQ; Mast cell; Vascular endothelial growth factor; PCR; ELISA
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2020.108444

Mast cells play a significant role in urticaria pathogenesis. It's evidenced that vitamin D has positive impact in chronic spontaneous urticaria (CSU) recently, but underlying mechanisms remain unclear. In this study, isobaric tag for relative and absolute quantification-liquid chromatography-mass spectrometer/mass spectrometer was used to detect the expression of proteins in sera of CSU patients and healthy subjects. Thirty-one differentially expressed proteins were identified, in which vitamin D binding protein (VDBP) was higher in CSU patients than that in healthy subjects after verification. Our results indicated that sera of CSU patients induced the production of vascular endothelial growth factor (VEGF) in mast cells through PI3K/Akt/p38 MAPK/HIF-1α axis in an IgE-depended way, and 25(OH)D3 suppressed the expression of VEGF by inhibiting this signaling pathway axis in this process. Collectively, these results suggest VDBP to be a potential biomarker and propose a potential mechanism of benefit for vitamin D therapy in CSU. Vitamin D can suppress the production of VEGF in mast cell by inhibiting PI3K/Akt/p38 MAPK/HIF-1α in chronic spontaneous urticaria: we analyzed the protein profile in serum of CSU, investigated the sera-induced VEGF expression in mast cell and the inhibition of vitamin D in it. CSU, chronic spontaneous urticaria; VDBP, vitamin D binding protein; VEGF, vascular endothelial growth factor. [Display omitted] •VDBP would be a potential biomarker for the chronic spontaneous urticaria.•25(OH)D3 suppressed the expression of VEGF induced by high-IgE sera of urticaria.•25(OH)D3 in urticaria acted through PI3K/Akt/p38 MAPK/HIF-1α pathway.•Vitamin D can facilitate the therapy of the chronic spontaneous urticaria.