Calcitonin gene-related peptide and intermedin induce phosphorylation of p44/42 MAPK in primary human lymphatic endothelial cells in vitro

Hasan, Shirin R.; Manolis, Dimitrios; Stephenson, Ewan; Ryskiewicz-Sokalska, Oktawia A.; Maraveyas, Anthony; Nikitenko, Leonid L.

Abstract

Calcitonin gene-related peptide (CGRP) and adrenomedullin 2/intermedin (AM2/IMD) play important roles in several pathologies, including cardiovascular disease, migraine and cancer. The efficacy of drugs targeting CGRP signalling axis for the treatment of migraine patients is sometimes offset by side effects (e.g. inflammation and microvascular complications, including aberrant neovascularisation in the skin). Recent studies using animal models implicate CGRP in lymphangiogenesis and lymphatic vessel function. However, whether CGRP or AM2/IMD can act directly on lymphatic endothelial cells is unknown. Here, we found that CGRP and AM2/IMD induced p44/42 MAPK phosphorylation in a time- and dose-dependent manner in primary human dermal lymphatic endothelial cells (HDLEC) in vitro, and thus directly affected these cells. These new findings reveal CGRP and AM2/IMD as novel regulators of LEC biology and warrant further investigation of their roles in the context of pathologies associated with lymphatic function in the skin and other organs, and therapies targeting CGRP signalling axis.

Citation

Hasan, S. R., Manolis, D., Stephenson, E., Ryskiewicz-Sokalska, O. A., Maraveyas, A., & Nikitenko, L. L. (2024). Calcitonin gene-related peptide and intermedin induce phosphorylation of p44/42 MAPK in primary human lymphatic endothelial cells in vitro. Cellular Signalling, 121, Article 111261. https://doi.org/10.1016/j.cellsig.2024.111261

• Journal Article Type: Article
• Acceptance Date: Jun 12, 2024
• Online Publication Date: Jun 15, 2024
• Publication Date: Sep 1, 2024
• Deposit Date: Jun 18, 2024
• Publicly Available Date: Jun 19, 2024
• Journal: Cellular Signalling
• Print ISSN: 0898-6568
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 121
• Article Number: 111261
• DOI: https://doi.org/10.1016/j.cellsig.2024.111261
• Keywords: Adrenomedullin; adrenomedullin 2; CGRP; intermedin; lymphatic endothelial cells; skin; p44/42 mitogen-activated kinases
• Public URL: https://hull-repository.worktribe.com/output/4711317