Insufficient autophagy in idiopathic pulmonary fibrosis
| العنوان: | Insufficient autophagy in idiopathic pulmonary fibrosis |
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| المؤلفون: | Naoki Takasaka, Kenji Kobayashi, Chikako Tsurushige, Noriki Kamiya, Makoto Kawaishi, Stephen L. Nishimura, Jun Kojima, Yoshinori Kawabata, Hiroshi Hano, Hiromichi Hara, Makoto Odaka, Haruhiko Yanagisawa, Jun Araya, Satoko Fujii, Katsutoshi Nakayama, Saburo Ito, Toshiaki Morikawa, Jun Hirano, Kazuyoshi Kuwano |
| المصدر: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 304:L56-L69 |
| بيانات النشر: | American Physiological Society, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Pulmonary and Respiratory Medicine, Senescence, Sequestosome-1 Protein, Physiology, Biology, Pathogenesis, Idiopathic pulmonary fibrosis, Physiology (medical), Autophagy, medicine, Humans, Myofibroblasts, Cellular Senescence, Adaptor Proteins, Signal Transducing, Ubiquitin, Tunicamycin, Signal transducing adaptor protein, Cell Differentiation, Epithelial Cells, Cell Biology, Endoplasmic Reticulum Stress, medicine.disease, Idiopathic Pulmonary Fibrosis, Cell biology, Myofibroblast, Homeostasis |
| الوصف: | Autophagy, a process that helps maintain homeostatic balance between the synthesis, degradation, and recycling of organelles and proteins to meet metabolic demands, plays an important regulatory role in cellular senescence and differentiation. Here we examine the regulatory role of autophagy in idiopathic pulmonary fibrosis (IPF) pathogenesis. We test the hypothesis that epithelial cell senescence and myofibroblast differentiation are consequences of insufficient autophagy. 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 human IPF biospecimens reveals that epithelial cells show increased cellular senescence, and both overlaying epithelial cells and fibroblasts in fibroblastic foci (FF) express both ubiquitinated proteins and p62. 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. |
| تدمد: | 1522-1504 1040-0605 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::215bcb3949bc5bf1d7ff67eff598ed6aTest https://doi.org/10.1152/ajplung.00213.2012Test |
| رقم الانضمام: | edsair.doi.dedup.....215bcb3949bc5bf1d7ff67eff598ed6a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221504 10400605 |
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