Mucin 4, expressed in the airways, suppresses neutrophilic inflammation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08163
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Jichi Medical University
• Principal Investigator: Ohta Hiromitsu 自治医科大学, 医学部, 講師 (40451562)
• Co-Investigator(Kenkyū-buntansha): 萩原 弘一 自治医科大学, 医学部, 教授 (00240705) ; 海老名 雅仁 東北医科薬科大学, 医学部, 教授 (10280885) ; 椎原 淳 自治医科大学, 医学部, 助教 (20737241)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: びまん性肺胞障害 / 肺障害 / Mucin 4 / 好中球性炎症

Outline of Final Research Achievements

Japanese people exhibit a high prevalence of severe lung injury, and previous studies have identified mucin (Muc4), which is expressed in airway epithelial cells, as the causative gene. Utilizing next-generation sequencing, we demonstrated that there are five principal allele types of the MUC4 gene and that nearly all patients possess the risk allele. Furthermore, the MUC4 gene was cloned and transfected into airway epithelial cells for expression. No difference in proliferative capacity or drug resistance was observed in the MUC4-expressing cells themselves. When the sugar chain portion of MUC4 was recovered and added to neutrophils, inhibition of cell death (netosis) was observed in normal control Mucin 4. However, the inhibition of cell death was weaker in the risk allele.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

今回の研究で重症肺障害のリスクとなるMucin4の遺伝子型が明らかになった。また、Mucin4の遺伝子型が好中球性炎症の重症化と関係することを示唆する結果が得られた。今回の研究は、重症肺障害の発症リスクをあらかじめ推定することに役立つものであり、また、日本人に多い重症肺障害の発症機序を解明するための一助になるものである。