The cell fate regulated by autophagy and ER stress in idiopathic pulmonary fibrosis.

特发性肺纤维化中自噬和内质网应激调节的细胞命运。

• 批准号: 23591162
• 负责人: ARAYA Jun
• 金额: $ 3.24万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591162/
• 关键词: オートファジー

Autophagy, a process of lysosomal degradation, plays an important regulatory role in cellular senescence and differentiation. Here we examine the regulatory role of autophagy in idiopathic pulmonary fibrosis (IPF) pathogenesis. Using biochemical evaluation of in vitro models, we find that autophagy inhibition is sufficient to induce acceleration of epithelial cell senescence and myofibroblast differentiation in lung fibroblasts. Immunohistochemical evaluation of IPF lungs reveals that epithelial cells show increased cellular senescence. Insufficient autophagy is demonstrated in both overlaying epithelial cells and fibroblasts in fibroblastic foci (FF). These findings suggest that insufficient autophagy is an underlying mechanism of both accelerated cellular senescence and myofibroblast differentiation in a cell-type specific manner and is a promising clue for understanding the pathogenesis of IPF.

自噬是一种溶酶体降解过程，在细胞衰老和分化中起着重要的调节作用。在这里，我们研究了自噬在特发性肺纤维化（IPF）发病机理中的调节作用。使用体外模型的生化评估，我们发现自噬抑制足以诱导肺成纤维细胞中上皮细胞衰老和肌纤维细胞分化的加速。 IPF肺的免疫组织化学评估表明，上皮细胞显示出细胞衰老的增加。在成纤维细胞（FF）中叠加上皮细胞和成纤维细胞中，自噬不足。这些发现表明，自噬不足是以细胞类型的特异性方式加速细胞衰老和肌纤维细胞分化的基本机制，并且是理解IPF发病机理的有希望的线索。

项目成果

Annuall Reiew 呼吸器

年度呼吸系统回顾

• 发表时间: 2013
• 作者: 荒屋 潤; 原 弘道;桑野和善
• 通讯作者: 桑野和善

Insufficient autophagy promotes bronchial epithelial cell senescence in chronic obstructive pulmonary disease

• DOI: 10.4161/0nci.20297
• 发表时间: 2014-01-01
• 期刊: OncoImmunology
• 影响因子: 7.2
• 作者: Fujii, S.;Hara, H.;Numata, T.
• 通讯作者: Numata, T.

Autophagy Induction by SIRT6 through Attenuation of Insulin-like Growth Factor Signaling Is Involved in the Regulation of Human Bronchial Epithelial Cell Senescence

• DOI: 10.4049/jimmunol.1302341
• 发表时间: 2014-02-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Takasaka, Naoki;Araya, Jun;Kuwano, Kazuyoshi
• 通讯作者: Kuwano, Kazuyoshi

Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence

• DOI: 10.1152/ajplung.00146.2013
• 发表时间: 2013-11-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
• 影响因子: 4.9
• 作者: Hara, Hiromichi;Araya, Jun;Kuwano, Kazuyoshi
• 通讯作者: Kuwano, Kazuyoshi

Insufficient autophagy in idiopathic pulmonary fibrosis

• DOI: 10.1152/ajplung.00213.2012
• 发表时间: 2013-01-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
• 影响因子: 4.9
• 作者: Araya, Jun;Kojima, Jun;Kuwano, Kazuyoshi
• 通讯作者: Kuwano, Kazuyoshi