Develpment of novel treatment focusing on the proprotein convertase in chronic lung disease of the premature infant

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K18005
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine; Pediatrics
• Research Institution: Nagoya City University
• Principal Investigator: Kato Shin 名古屋市立大学, 医薬学総合研究院(医学), 助教 (90551250)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 慢性肺疾患 / 早産児 / 肺胞形成 / 前駆タンパク質転換酵素 / myofibroblast

Outline of Final Research Achievements

We hypothesized that furin, also known as an enzyme that cleaves proproteins of factors involved in alveologenesis, may play a key role in the pathogenesis of chronic lung disease in preterm infants. Here we examined its role using a chronic lung disease model in neonatal mice exposed to 85% oxygen. We showed that furin is expressed in myofibroblasts in mouse lungs, and that the expression of furin and its target proteins is decreased in the mouse model, resulting in worsened alveoli formation. Next, we showed that administration of a furin inhibitor successfully reproduced the pathology. Finally, we showed that treatment with furin improved alveoli formation in a hyperoxia-exposed mouse model.

Free Research Field

新生児学、新生児呼吸器病学

Academic Significance and Societal Importance of the Research Achievements

本研究で我々は、早産児に特有の慢性肺疾患の病因として、新規にfurinが重要な役割を果たしていることを世界で初めて明らかにした。標準治療では改善が困難な重症の慢性肺疾患において、新規治療戦略の選択肢となりうる。毎年およそ1200人前後と推計される罹患児の長期予後の改善から社会参画の促進や医療費の抑制につながることも期待できるなど、社会的意義が非常に大きい。