ArticleJCI insight2019
Secretion of leukotrienes by senescent lung fibroblasts promotes pulmonary fibrosis.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 119 citations in OpenAlex.
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- DPEP1 promotes pulmonary fibrosis by regulating arachidonic acid metabolism.Journal of thoracic disease · 2026Article
- Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.Ageing research reviews · 2026Review
- Host-Pathogen Interaction as a Driver of Cellular Senescence: Microbial Triggers and Host Response.International journal of molecular sciences · 2026Review
- Dynamic tRNA modification landscapes reveal METTL1 in fibroblasts as a central regulator of aging.Science China. Life sciences · 2026Article
- Multi-omic analysis reveals Wharton's jelly mesenchymal stem cells shift the pro-inflammatory phenotype of fibroblast subpopulation to induce skin rejuvenation.Cell & bioscience · 2026Article
- Diabetic Wound Vasculopathy and Neuropathy: Spotlight on Wound Lipid Signaling.Advances in wound care · 2026Review
- Loss of sirtuin 3 disrupts cellular senescence signaling pathways.GeroScience · 2026Article
- Article
- Intracellular NADJournal of cellular and molecular medicine · 2026Article
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Lung mTOR activation leads to lung fibrosis or emphysema via senescence of specific lung cells.Scientific reports · 2026Article
- Analysis of Intracellular Fatty Acid Metabolism during Doxorubicin-Induced Senescence of MCF7 Cells Using Raman Imaging.ACS omega · 2026Article
- Beyond attenuation: a translational review of curative-intent pharmacological targets in idiopathic pulmonary fibrosis.Frontiers in medicine · 2026Review
- The drug discovery and therapeutic nano-strategies targeting cellular senescence.Materials today. Bio · 2025Review
- Fatty Acids Dysregulation Correlates with Lung Function in Idiopathic Pulmonary Fibrosis.Lung · 2025Article
- Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.International journal of molecular sciences · 2025Review
- Anti-senescence therapies: a new concept to address cardiovascular disease.Cardiovascular research · 2025Review
- Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective.Frontiers of medicine · 2025Review
- Autophagy in Tissue Repair and Regeneration.Cells · 2025Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Accumulation of senescent cells is associated with the progression of pulmonary fibrosis, but mechanisms accounting for this linkage are not well understood. To explore this issue, we investigated whether a class of biologically active profibrotic lipids, the leukotrienes (LT), is part of the senescence-associated secretory phenotype. The analysis of conditioned medium (CM), lipid extracts, and gene expression of LT biosynthesis enzymes revealed that senescent cells secreted LT, regardless of the origin of the cells or the modality of senescence induction. The synthesis of LT was biphasic and followed by antifibrotic prostaglandin (PG) secretion. The LT-rich CM of senescent lung fibroblasts (IMR-90) induced profibrotic signaling in naive fibroblasts, which were abrogated by inhibitors of ALOX5, the principal enzyme in LT biosynthesis. The bleomycin-induced expression of genes encoding LT and PG synthases, level of cysteinyl LT in the bronchoalveolar lavage, and overall fibrosis were reduced upon senescent cell removal either in a genetic mouse model or after senolytic treatment. Quantification of ALOX5+ cells in lung explants obtained from idiopathic pulmonary fibrosis (IPF) patients indicated that half of these cells were also senescent (p16Ink4a+). Unlike human fibroblasts from unused donor lungs made senescent by irradiation, senescent IPF fibroblasts secreted LTs but failed to synthesize PGs. This study demonstrates for the first time to our knowledge that senescent cells secrete functional LTs, significantly contributing to the LT pool known to cause or exacerbate IPF.
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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.