LTBP4 has a critical role in the pathogenesis of emphysema as the age-related disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The University of Tokyo
• Principal Investigator: Ishii Masaki 東京大学, 医学部附属病院, 講師 (20724438)
• Co-Investigator(Kenkyū-buntansha): 山口 泰弘 自治医科大学, 医学部, 教授 (60376473)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肺気腫 / LTBP-4

Outline of Final Research Achievements

LTBP4 belongs to the LTBP family of proteins and plays an important role as a structural component of extracellular matrix. LTBP4-related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema and other evidence of a generalized connective tissue disorder as the age-related disease. However, the role of LTBP4 remains unclear in the pathogenesis of emphysema.
RT-PCR analysis showed that the decreased expression of elastin and increased expression of TNF-α, MMP and TIMP-1 were observed in human lung fibroblast cells by siRNA treatment. The cell contraction assay demonstrated the decreased level of elasticity and the increase of SAβ-gal staining of cells were observed. The shotgun proteomics and RT-PCR showed that the oxidoreductases such as SOD and GSTM3 were decreased in the treatment LTBP4 siRNA by using exosome of cell culture supernatant.

Free Research Field

老年医学

Academic Significance and Societal Importance of the Research Achievements

LTBP-4はelastinによる肺弾性線維形成や肺弾性収縮力の維持に必要であるほか、ミトコンドリア機能保持を介した抗炎症・抗酸化効果、抗老化の役割を担い、肺気腫進展予防も含めた肺組織再生の上で、重要な因子である可能性が示唆された。