Age-related diseases analyzed by ER stresses and immune functions using murine models including iPSCs

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293166
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Nagoya Women's University (2015-2016); Nagoya University (2013-2014)
• Principal Investigator: isobe ken-ichi 名古屋女子大学, 家政学部, 教授 (20151441)
• Co-Investigator(Kenkyū-buntansha): 祖父江 元 名古屋大学, 医学(系)研究科(研究院), 教授 (20148315) ; 大橋 憲太郎 岐阜大学, 工学部, 准教授 (50332953) ; 伊藤 佐知子 名古屋大学, 医学(系)研究科(研究院), 助教 (70447845) ; 西尾 尚美 名古屋大学, 医学(系)研究科(研究院), 助教 (80513457)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 老化 / GADD34 / ERストレス

Outline of Final Research Achievements

We intended to analyze age-related disease from the points of ER stresses and immune responses. Acrolein, which is abundant in cigarette smoke, and cooking emission,
plays a major role in COPD . Acrolein induced the expression of GADD34 and acute inflammation in airways, which followed COPD. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. We examine the effects of GADD34 on natural life span by using GADD34-deficient mice. We found that with age GADD34-deficient mice become obese, developing fatty liver followed by liver cirrhosis, hepatocellular carcinoma, and insulin resistance.　 GADD34　suppresses insulin signaling in young mice. However, by aging macrophages in fat tissues work to induce insulin resistance. We succeeded to differentiate to various tissue cells from iPSCs established from aged mice, which may repair damaged tissues by age-related diseases.

Free Research Field

免疫学、老化学