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Insufficient autophagy in idiopathic pulmonary fibrosis
- Source :
- American Journal of Physiology-Lung Cellular and Molecular Physiology. 304:L56-L69
- Publication Year :
- 2013
- Publisher :
- American Physiological Society, 2013.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15221504 and 10400605
- Volume :
- 304
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Accession number :
- edsair.doi.dedup.....215bcb3949bc5bf1d7ff67eff598ed6a