Regulation of sensory nerve system in lymphangigenesis and lymph edema

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16994
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Kitasato University
• Principal Investigator: Mishima Toshiaki 北里大学, 医学部, 講師 (00296477)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: リンパ浮腫 / 神経ペプチド

Outline of Final Research Achievements

Secondary lymphedema commonly arises as a complication of cancer surgery and radiation treatment; however, the underlying mechanisms are poorly understood. 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. Lymphedema in RAMP1-/- mice was sustained, with suppressed lymphangiogenesis and reduced expression of vascular endothelial growth factor (VEGF)-C and VEGFR-3. The number of pro-inflammatory macrophages in RAMP1-/- mice was higher than that in WT mice. RAMP1 signaling improves lymphedema and accelerates lymphangiogenesis associated with reduced recruitment of pro-inflammatory macrophages.

Free Research Field

血管外科

Academic Significance and Societal Importance of the Research Achievements

乳がんの腋窩リンパ節廓清術後、子宮・卵巣がんの骨盤内リンパ節廓清術後、またこれらに追加される放射線療法後などの患者では2次性のリンパ浮腫が発症することがある。多くは難治性で慢性化するだけでなく、皮膚の広範な肥厚と線維化、繰り返す蜂窩織炎などのために患者のQOLは著しく損なわれる。現在でも本質的な治療方法はないため、リンパ再生を含めたリンパ管新生増強方策が切望されている。この点、CGRPや特異的RAMP1アゴニストが2次性リンパ浮腫の治療に有効であることが期待される。