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Insufficient autophagy in idiopathic pulmonary fibrosis.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2013 Jan 01; Vol. 304 (1), pp. L56-69. Date of Electronic Publication: 2012 Oct 19. - Publication Year :
- 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 :
- Adaptor Proteins, Signal Transducing biosynthesis
Cell Differentiation physiology
Cellular Senescence physiology
Endoplasmic Reticulum Stress physiology
Epithelial Cells pathology
Epithelial Cells physiology
Humans
Myofibroblasts cytology
Sequestosome-1 Protein
Tunicamycin pharmacology
Ubiquitin biosynthesis
Autophagy
Idiopathic Pulmonary Fibrosis physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 304
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 23087019
- Full Text :
- https://doi.org/10.1152/ajplung.00213.2012