Overexpression of Daam-1 on pulmonary arterial wall for the pathogenesis of human idiopathic pulmonary arterial hypertension

2017 Fiscal Year Final Research Report

• Project/Area Number: 26460460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Toho University
• Principal Investigator: WAKAYAMA Megumi 東邦大学, 医学部, 講師 (40230924)
• Co-Investigator(Kenkyū-buntansha): 渋谷 和俊 東邦大学, 医学部, 教授 (20196447)
• Research Collaborator: YANAI Shun ; SHIMODAIRA Kayoko ; SHINOZAKI Minoru
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 特発性肺動脈性肺高血圧症 / Wnt/PCPパスウェイ / Daam-1 / Dvl-2 / 肺動脈中膜平滑筋細胞

Outline of Final Research Achievements

Evidence from our recent study suggests that idiopathic pulmonary arterial hypertension (IPAH) pathogenesis is related to upregulation of the Wnt/PCP pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins - namely Wnt-11, Dvl-2, and Daam-1 - in pulmonary arteries.
We analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained 9 IPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary arterial abnormalities, and marked expression of Dvl-2 and Daam-1 was confirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in contrast with specimens from associated pulmonary arterial hypertension cases and controls. So it was suggested that high Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH.

Free Research Field

人体病理、外科病理、真菌症の病理