ArticleAmerican journal of respiratory cell and molecular biology2018
Inhibition of Phosphoglycerate Dehydrogenase Attenuates Bleomycin-induced Pulmonary Fibrosis.
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 44 papers.
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44 citing papers in PubMed, 80 citations in OpenAlex.
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Article
- PHGDH mediated serine biosynthesis metabolism suppresses vascular calcification.Biology direct · 2026Article
- Bleomycin-induced lung fibrosis and dysfunction is exacerbated by G6PD deficiency.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Mitochondrial one-carbon metabolism is required for TGF-β-induced glycine synthesis and fibrotic responses.Nature communications · 2025Article
- Pyruvate kinase splice variants in fibroblasts influence cardiac remodeling after myocardial infarction in male mice.Journal of molecular and cellular cardiology · 2025Article
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 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
- mTOR signaling regulates multiple metabolic pathways in human lung fibroblasts after TGF-β and in pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- L-serine metabolic regulation and host respiratory homeostasis.Frontiers in cellular and infection microbiology · 2025Review
- Metabolic reprogramming and therapeutic targeting in non-small cell lung cancer: emerging insights beyond the Warburg effect.Frontiers in oncology · 2025Review
- Metabolic control of collagen synthesis.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- [A transcriptomic analysis of correlation between mitochondrial function and energy metabolism remodeling in mice with myocardial fibrosis following myocardial infarction].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Fibrotic pathways and fibroblast-like synoviocyte phenotypes in osteoarthritis.Frontiers in immunology · 2024Review
- Effects of caloric restriction and ketogenic diet on renal fibrosis after ischemia/reperfusion injury.Heliyon · 2023Article
- Integrating inflammatory biomarker analysis and artificial-intelligence-enabled image-based profiling to identify drug targets for intestinal fibrosis.Cell chemical biology · 2023Article
- Dietary Manipulation of Amino Acids for Cancer Therapy.Nutrients · 2023Review
- Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform.iScience · 2023Article
- A Transcriptomic Regulatory Network among miRNAs, lncRNAs, circRNAs, and mRNAs Associated with L-leucine-induced Proliferation of Equine Satellite Cells.Animals : an open access journal from MDPI · 2023Article
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15 authors at 2 institutions in 1 country.
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Abstract
Organ fibrosis, including idiopathic pulmonary fibrosis, is associated with significant morbidity and mortality. Because currently available therapies have limited effect, there is a need to better understand the mechanisms by which organ fibrosis occurs. We have recently reported that transforming growth factor (TGF)-β, a key cytokine that promotes fibrogenesis, induces the expression of the enzymes of the de novo serine and glycine synthesis pathway in human lung fibroblasts, and that phosphoglycerate dehydrogenase (PHGDH; the first and rate-limiting enzyme of the pathway) is required to promote collagen protein synthesis downstream of TGF-β. In this study, we investigated whether inhibition of de novo serine and glycine synthesis attenuates lung fibrosis in vivo. We found that TGF-β induces mRNA and protein expression of PHGDH in murine fibroblasts. Similarly, intratracheal administration of bleomycin resulted in increased expression of PHGDH in mouse lungs, localized to fibrotic regions. Using a newly developed small molecule inhibitor of PHGDH (NCT-503), we tested whether pharmacologic inhibition of PHGDH could inhibit fibrogenesis both in vitro and in vivo. Treatment of murine and human lung fibroblasts with NCT-503 decreased TGF-β-induced collagen protein synthesis. Mice treated with the PHGDH inhibitor beginning 7 days after intratracheal instillation of bleomycin had attenuation of lung fibrosis. These results indicate that the de novo serine and glycine synthesis pathway is necessary for TGF-β-induced collagen synthesis and bleomycin-induced pulmonary fibrosis. PHGDH and other enzymes in the de novo serine and glycine synthesis pathway may be a therapeutic target for treatment of fibrotic diseases, including idiopathic pulmonary fibrosis.
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