ArticleAmerican journal of respiratory cell and molecular biology2018
Lipid Synthesis Is Required to Resolve Endoplasmic Reticulum Stress and Limit Fibrotic Responses in the Lung.
Article in American journal of respiratory cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Lipodystrophy and adipose tissue recovery are mediated by the Wnt/lipogenesis axis during skin fibrosis.The Journal of pathology · 2026Article
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Integrated Analysis of the Lung Microbiome and Metabolome Reveals Associations Between Amino Acid Metabolism and Pulmonary Fibrosis in a Bleomycin-Induced Mouse Model.International journal of molecular sciences · 2026Article
- CSE Induces Lung Epithelial Cell-derived Exosomal LINC01133-mediated FOXA1 Activity Through SRSF6 to Affect MRC-5 Cellular Lipid Metabolism and Autophagy.Applied biochemistry and biotechnology · 2026Article
- The metabolic code of pulmonary disease: from mechanisms to therapeutic opportunities.Breathe (Sheffield, England) · 2026Review
- Combined HDL-BMI Phenotyping Provides Incremental Prognostic Value in Idiopathic Pulmonary Fibrosis.Journal of clinical medicine · 2026Article
- Lipid metabolism as a cell-state determinant in pulmonary fibrosis: from epithelial failure to ferroptosis-driven amplification.Frontiers in pharmacology · 2026Review
- Atgl-Dependent Adipocyte Lipolysis Promotes Lipodystrophy and Restrains Fibrogenic Responses during Skin Fibrosis.The Journal of investigative dermatology · 2025Article
- Exploring ABHD5 as a Lipid-Related Biomarker in Idiopathic Pulmonary Fibrosis: Integrating Machine Learning, Bioinformatics, and In Vitro Experiments.Inflammation · 2025Article
- Influence of metabolic factors on systemic sclerosis complicated with severe interstitial lung disease based on high-resolution computed tomography grading.Clinical rheumatology · 2025Article
- PPARs: modulating lipotoxicity and thus inhibiting fibrosis.Hormones (Athens, Greece) · 2025Review
- Targeting alveolar epithelial cell metabolism in pulmonary fibrosis: Pioneering an emerging therapeutic strategy.Frontiers in cell and developmental biology · 2025Review
- The role of SIRT1 in kidney diseases.International urology and nephrology · 2025Review
- Lipid Deficiency Contributes to Impaired Alveolar Progenitor Cell Function in Aging and Idiopathic Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- Lipids to the Rescue in Pulmonary Fibrosis: Biosynthesis, Bioenergetics, or Epigenetics?American journal of respiratory cell and molecular biology · 2024Article
- The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases.Lipids in health and disease · 2024Review
- Exercise mitigates flow recirculation and activates metabolic transducer SCD1 to catalyze vascular protective metabolites.Science advances · 2024Article
- Circulating metabolic profile in idiopathic pulmonary fibrosis: data from the IPF-PRO Registry.Respiratory research · 2024Observational
- Lipid metabolism in idiopathic pulmonary fibrosis: From pathogenesis to therapy.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Overexpression of fatty acid synthase attenuates bleomycin induced lung fibrosis by restoring mitochondrial dysfunction in mice.Scientific reports · 2023Article
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
Endoplasmic reticulum (ER) stress is evident in the alveolar epithelium of humans and mice with pulmonary fibrosis, but neither the mechanisms causing ER stress nor the contribution of ER stress to fibrosis is understood. A well-recognized adaptive response to ER stress is that affected cells induce lipid synthesis; however, we recently reported that lipid synthesis was downregulated in the alveolar epithelium in pulmonary fibrosis. In the present study, we sought to determine whether lipid synthesis is needed to resolve ER stress and limit fibrotic remodeling in the lung. Pharmacologic and genetic manipulations were performed to assess whether lipid production is required for resolving ER stress and limiting fibrotic responses in cultured alveolar epithelial cells and whole-lung tissues. Concentrations of ER stress markers and lipid synthesis enzymes were also measured in control and idiopathic pulmonary fibrosis lung tissues. We found that chemical agents that induce ER stress (tunicamycin or thapsigargin) enhanced lipid production in cultured alveolar epithelial cells and in the mouse lung. Moreover, lipid production was found to be dependent on the enzyme stearoyl-coenzyme A desaturase 1, and when pharmacologically inhibited, ER stress persisted and lung fibrosis ensued. Conversely, lipid production was reduced in mouse and human fibrotic lung, despite there being an increase in the magnitude of ER stress. Furthermore, augmenting lipid production effectively reduced ER stress and mitigated fibrotic remodeling in the mouse lung after exposure to silica. Augmenting lipid production reduces ER stress and attenuates fibrotic remodeling in the mouse lung, suggesting that similar approaches might be effective for treating human fibrotic lung diseases.
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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.