ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Therapeutic targeting of argininosuccinate synthase 1 (ASS1)-deficient pulmonary fibrosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 44 citations in OpenAlex.
- The Gut-Lung Microbiome Axis in Alveolar Stem Cell Regeneration and Lung Repair.Microorganisms · 2026Review
- TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis.JCI insight · 2026Article
- Clinical and transcriptomic risk factors for post-tuberculosis lung disease in a cohort of Kenyan adults.American journal of respiratory and critical care medicine · 2026Observational
- Unraveling the fibrotic microenvironment in intrauterine adhesions through integrated metabolomics and proteomics.BMC women's health · 2026Article
- RNA helicase SKIV2L impedes tumor immunity by reprogramming arginine metabolism of hepatocellular carcinomas.Journal for immunotherapy of cancer · 2026Article
- Circadian Dysregulation in Aging Alters Senescence and Inflammatory Pathways in a Sex- and Time-of-Day-Dependent Manner.bioRxiv : the preprint server for biology · 2026Article
- SENP3 promotes renal tubular epithelial cell apoptosis after ischemia-reperfusion injury via ASS1 deSUMOylation.Cell death & disease · 2025Article
- Altered Metabolism in Idiopathic Pulmonary Fibrosis.Journal of cellular physiology · 2025Review
- Exploring the potential mechanisms of anti-pulmonary fibrosis effects of Luo Han Guo via network pharmacology, molecular docking, and experimental validation.Scientific reports · 2025Article
- EGOI-PCOS survey on the prevalence of respiratory disorders associated with polycystic ovary syndrome.Multidisciplinary respiratory medicine · 2025Article
- Repurposing flavopiridol as an inhaled therapeutic for pulmonary fibrosis.European journal of pharmacology · 2025Article
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 2025Review
- Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.Cell communication and signaling : CCS · 2025Review
- Arginine promotes the activation of human lung fibroblasts independent of its metabolism.The Biochemical journal · 2025Article
- Kynurenine acts as a signaling molecule to attenuate pulmonary fibrosis by enhancing the AHR-PTEN axis.Journal of advanced research · 2025Article
- Spatial and Single-Cell Transcriptomics Reveals the Regional Division of the Spatial Structure of MASH Fibrosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Cardiopulmonary bypass with deep hypothermic circulatory arrest results in organ-specific transcriptomic responses in pediatric swine.Translational research : the journal of laboratory and clinical medicine · 2025Article
- Identification of potential biomarkers and pathways involved in high-altitude pulmonary edema using GC-MS and LC-MS metabolomic methods.Scientific reports · 2024Article
- Noninvasive biomarkers implicated in urea and TCA cycles for metabolic liver disease.Biomarker research · 2024Article
- Triangle correlations of lung microbiome, host physiology and gut microbiome in a rat model of idiopathic pulmonary fibrosis.Scientific reports · 2024Article
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8 authors at 1 institution in 1 country.
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Abstract
Argininosuccinate synthase 1 (ASS1) serves as a critical enzyme in arginine biosynthesis; however, its role in interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), remains largely unknown. This study aims at characterization and targeting of ASS1 deficiency in pulmonary fibrosis. We find that ASS1 was significantly decreased and inversely correlated with fibrotic status. Transcriptional downregulation of ASS1 was noted in fibroblastic foci of primary lung fibroblasts isolated from IPF patients. Genetic manipulations of ASS1 studies confirm that ASS1 expression inhibited fibroblast cell proliferation, migration, and invasion. We further show that the hepatocyte growth factor receptor (Met) receptor was activated and acted upstream of the Src-STAT3 axis signaling in ASS1-knockdown fibroblasts. Interestingly, both arginine-free conditions and arginine deiminase treatment were demonstrated to kill fibrotic fibroblasts, attenuated bleomycin-induced pulmonary fibrosis in mice, as well as synergistically increased nintedanib efficacy. Our data suggest ASS1 deficiency as a druggable target and also provide a unique therapeutic strategy against pulmonary fibrosis.
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