The role of vascular endothelial growth factor receptor-1 signaling in compensatory contralateral lung growth following unilateral pneumonectomy.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10688
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kitasato University
• Principal Investigator: Matsui Yoshio 北里大学, 医学部, 助教 (00365123)
• Co-Investigator(Kenkyū-buntansha): 天野 英樹 北里大学, 医学部, 講師 (60296481) ; 江島 耕二 北里大学, 医学部, 准教授 (30327324)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肺再生 / VEGF / VEGFR1

Outline of Final Research Achievements

Vascular endothelial growth factor (VEGF) and its receptors promote lung regeneration. The present study was to examine the role of VEGF receptor 1 (VEGFR1) signaling in lung regeneration after pneumonectomy. After left pneumonectomy, the right lung weight was higher in VEGF transgenic mice than wild-type (WT) mice and was suppressed significantly in mice injected with a VEGF neutralizing antibody and in VEGF receptor-1 tyrosine kinase-deficient mice (TK-/- mice). The mobilization of progenitor cells expressing VEGFR1+ cells from bone marrow and the recruitment of these cells to lung tissue were also suppressed in the TK-/- mice. WT mice transplanted with bone marrow from TK-/- transgenic GFP+ mice had significantly lower numbers of GFP+/aquaporin 5 +, , GFP+/surfactant protein A+, and GFP+/VEGFR1+ cells than WT mice transplanted with bone marrow from WTGFP+ mice. Overall, these results suggest that VEGF signaling contributes to compensatory lung growth by mobilizing VEGFR1+ cells.

Free Research Field

呼吸器外科

Academic Significance and Societal Importance of the Research Achievements

片肺摘出の刺激によりVEGFR1チロシンキナーゼシグナルが骨髄組織のストローマ因子を活性化させ、骨髄組織からVEGFR1陽性細胞が動員され肺に集積しVEGFの産生を促すことで肺の代償性再生を増強している可能性が示唆された。本研究の成果は、骨髄由来のVEGFR-1発現細胞の気管内もしくは静脈内投与が、肺再生に関する新たな治療法になり得ることが期待される。