ArticleThe Journal of biological chemistry2015
Enhancing Autophagy with Drugs or Lung-directed Gene Therapy Reverses the Pathological Effects of Respiratory Epithelial Cell Proteinopathy.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Next-Generation Regenerative Therapies for Alpha-1 Antitrypsin Deficiency: Molecular Pathogenesis to Clinical Translation.International journal of molecular sciences · 2025Review
- Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.Cell reports. Medicine · 2025Article
- Liver gene therapy: The magic bullet for the sick lung.Molecular therapy. Methods & clinical development · 2022Article
- The Role of Decorin Proteoglycan in Mitophagy.Cancers · 2022Review
- Proteoglycan-driven Autophagy: A Nutrient-independent Mechanism to Control Intracellular Catabolism.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Childhood rare lung disease in the 21st century: "-omics" technology advances accelerating discovery.Pediatric pulmonology · 2020Review
- Endoplasmic reticulum stress and glutathione therapeutics in chronic lung diseases.Redox biology · 2020Review
- Lysosome biogenesis in health and disease.Journal of neurochemistry · 2019Review
- Adapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2019Review
- Quantitative Systems Pharmacological Analysis of Drugs of Abuse Reveals the Pleiotropy of Their Targets and the Effector Role of mTORC1.Frontiers in pharmacology · 2019Article
- Expression of mutant Sftpc in murine alveolar epithelia drives spontaneous lung fibrosis.The Journal of clinical investigation · 2018Article
- TFEB activation protects against cardiac proteotoxicity via increasing autophagic flux.Journal of molecular and cellular cardiology · 2017Article
- Autophagy modulation: a potential therapeutic approach in cardiac hypertrophy.American journal of physiology. Heart and circulatory physiology · 2017Review
- Master Autophagy Regulator Transcription Factor EB Regulates Cigarette Smoke-Induced Autophagy Impairment and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis.Antioxidants & redox signaling · 2017Article
- AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Disrupted autophagy undermines skeletal muscle adaptation and integrity.Mammalian genome : official journal of the International Mammalian Genome Society · 2016Review
- α1-antitrypsin Deficiency: A Misfolded Secretory Protein Variant with Unique Effects on the Endoplasmic Reticulum.Endoplasmic reticulum stress in diseases · 2016Article
- Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Differential regulation of autophagy and mitophagy in pulmonary diseases.American journal of physiology. Lung cellular and molecular physiology · 2016Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Recent studies have shown that autophagy mitigates the pathological effects of proteinopathies in the liver, heart, and skeletal muscle but this has not been investigated for proteinopathies that affect the lung. This may be due at least in part to the lack of an animal model robust enough for spontaneous pathological effects from proteinopathies even though several rare proteinopathies, surfactant protein A and C deficiencies, cause severe pulmonary fibrosis. In this report we show that the PiZ mouse, transgenic for the common misfolded variant α1-antitrypsin Z, is a model of respiratory epithelial cell proteinopathy with spontaneous pulmonary fibrosis. Intracellular accumulation of misfolded α1-antitrypsin Z in respiratory epithelial cells of the PiZ model resulted in activation of autophagy, leukocyte infiltration, and spontaneous pulmonary fibrosis severe enough to elicit functional restrictive deficits. Treatment with autophagy enhancer drugs or lung-directed gene transfer of TFEB, a master transcriptional activator of the autophagolysosomal system, reversed these proteotoxic consequences. We conclude that this mouse is an excellent model of respiratory epithelial proteinopathy with spontaneous pulmonary fibrosis and that autophagy is an important endogenous proteostasis mechanism and an attractive target for therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.