Files and links (1)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Lipid Synthesis Is Required to Resolve Endoplasmic Reticulum Stress and Limit Fibrotic Responses in the Lung
American journal of respiratory cell and molecular biology, v 59(2), pp 225-236
Aug 2018
PMID: 29465261
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
Metrics
Details
- Title
- Lipid Synthesis Is Required to Resolve Endoplasmic Reticulum Stress and Limit Fibrotic Responses in the Lung
- Creators
- Freddy Romero - Center for Translational Molecular MedicineXu Hong - 3 Medical Research Center, North China University of Science and Technology, Tangshan, ChinaDilip Shah - Center for Translational Molecular MedicineCaleb B Kallen - 4 Department of Obstetrics and Gynecology, and.Ivan Rosas - Brigham and Women's HospitalZhi Guo - Jinan Military General HospitalDeLeila Schriner - 2 Jane and Leonard Korman Lung CenterJulie Barta - Center for Translational Molecular MedicineHoora Shaghaghi - Center for Translational Molecular MedicineJan B Hoek - Thomas Jefferson UniversityClementina Mesaros - University of PennsylvaniaAugustine M Choi - Presbyterian HospitalNathaniel W Snyder - Drexel UniversityRoss Summer - Center for Translational Molecular Medicine
- Publication Details
- American journal of respiratory cell and molecular biology, v 59(2), pp 225-236
- Grant note
- P30 ES013508 / National Institute of Environmental Health Sciences K22 ES026235 / National Institute of Environmental Health Sciences R01 HL105490 / National Heart, Lung, and Blood Institute R01 HL131784 / National Heart, Lung, and Blood Institute
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics; A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000440609400014
- Scopus ID
- 2-s2.0-85051091378
- Other Identifier
- 991019167956204721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Respiratory System