Journal of Inflammation Research (Oct 2024)

Vascular Endothelial Growth Factor a Promotes Chronic Itch via VEGFA-VEGFR2-PI3K-TRPV1 Axis in Allergic Contact Dermatitis

  • Liu QY,
  • Liu HF,
  • Ye LQ,
  • Li T,
  • Chen ZM,
  • Wang Y,
  • Peng Z,
  • Wan L

Journal volume & issue
Vol. Volume 17
pp. 7423 – 7439

Abstract

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Qin-Yu Liu,1,2 Hua-Feng Liu,1,2 Liu-Qing Ye,1,2 Tian Li,1,2 Zuo-Ming Chen,1,2 Yu Wang,1,2 Zhe Peng,1,2 Li Wan1 1Department of Pain Medicine, The State Key Clinical Specialty in Pain Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China; 2Central Laboratory, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of ChinaCorrespondence: Li Wan, Email [email protected]: Allergic contact dermatitis (ACD), a prevalent skin disorder affecting up to 20% of the population, triggers significant discomfort and health implications. Our research investigates the pivotal role of Vascular Endothelial Growth Factor A (VEGFA) in chronic itching associated with ACD.Methods: Bioinformatics methods were utilized to identify differentially expressed genes (DEGs) between ACD models and patients. In vivo models of chronic pruritus in mice induced by 2,4-dinitrofluorobenzene (DNFB) were employed. Mice were administered subcutaneously with a VEGFA inhibitor, sFlt1, and compared to a control group. Real-time RT-PCR, Western blot, and immunohistochemical staining were performed to evaluate VEGFA expression and the impact of sFlt1 on itching behavior.Results: The analysis revealed that VEGFA is significantly upregulated in ACD skin, primarily expressed by keratinocytes. Administration of the VEGFA inhibitor sFlt1 in the ACD mouse model led to a substantial reduction in scratching behavior, indicating that VEGFA may mediate pruritus through the VEGFA-VEGFR2-PI3K-TRPV1 signaling pathway.Discussion: These findings suggest that VEGFA plays a crucial role in ACD-associated pruritus and may serve as a potential therapeutic target. However, further research is required to validate these findings and to explore additional molecular pathways involved in the pruritic response in ACD.Keywords: VEGFA, itch, allergic contact dermatitis, keratinocyte, VEGFR2

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