RAMP1 signaling improves lymphedema and promotes lymphangiogenesis in mice

The Journal of Surgical Research
Toshiaki MishimaMasataka Majima

Abstract

Secondary lymphedema commonly arises as a complication of cancer surgery and radiation treatment; however, the underlying mechanisms are poorly understood. Receptor activity-modifying protein 1 (RAMP1) forms a complex with calcitonin receptor-like receptor to generate the receptor for calcitonin gene-related peptide. The present study examined whether RAMP1 plays a role in increased lymphangiogenesis during secondary lymphedema. A model of lymphedema was generated by surgical removal of pre-existing lymphatic vessels from the subcutaneous tissue on the tails of RAMP1-deficient (RAMP1-/-) mice and their wild-type (WT) counterparts. The maximum diameter of the tail, lymphangiogenesis, and macrophage recruitment were then examined. Compared with that in WT mice, lymphedema in the tails in RAMP1-/- mice was sustained, with suppressed lymphangiogenesis and reduced expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor 3 at the distal edge of the lesions. The newly formed lymphatic vessels in RAMP1-/- mice were dilated, with impaired lymphatic flow. RAMP1 was expressed by macrophages recruited into edematous tail tissues distal to the wound. The number of macrophages in RAMP1-/- mice was hi...Continue Reading

Citations

Jan 9, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Seri TsuruMasataka Majima
Nov 22, 2018·PloS One·Tomoyoshi InoueMasataka Majima
Aug 28, 2020·World Journal of Stem Cells·Li-Ru Hu, Jian Pan
Jun 3, 2021·Neurology and Therapy·Andrew BlumenfeldIra Turner
Jun 16, 2021·Advances in Wound Care·Jerry F HsuAlex K Wong

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