ArticleJCI insight2023
The mRNA-binding protein DDX3 mediates TGF-β1 upregulation of translation and promotes pulmonary fibrosis.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- P7C3 alleviates hepatic fibrosis via targeting eIF4A1-mediated protein translation and autophagy in hepatic stellate cells.Archives of pharmacal research · 2026Article
- Genetic susceptibility to PMFrontiers in immunology · 2026Article
- Degradation System: Sialidase.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Sialidases as Potential Therapeutic Targets for Treatment of a Number of Human Diseases.International journal of molecular sciences · 2025Review
- New therapeutic approaches for fibrosis: harnessing translational regulation.Trends in molecular medicine · 2025Review
- Arginine promotes the activation of human lung fibroblasts independent of its metabolism.The Biochemical journal · 2025Article
- Snijders Blok-Campeau Syndrome Associated with Pulmonary Arterial Hypertension: A Case Report.Reports (MDPI) · 2025Article
- Review
- Capsaicin ameliorate pulmonary fibrosis via antioxidant Nrf-2/ PPAR- γ pathway activation and inflammatory TGF-β1/ NF-κB/COX II pathway inhibition.Frontiers in pharmacology · 2024Article
- Article
- Sialic acids Neu5Ac and KDN in adipose tissue samples from individuals following habitual vegetarian or non-vegetarian dietary patterns.Scientific reports · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary fibrosis is potentiated by a positive feedback loop involving the extracellular sialidase enzyme neuraminidase 3 (NEU3) causing release of active TGF-β1 and TGF-β1 upregulating NEU3 by increasing translation without affecting mRNA levels. In this report, we elucidate the TGF-β1 upregulation of the translation mechanism. In human lung fibroblasts, TGF-β1 increased levels of proteins, including NEU3, by increasing translation of the encoding mRNAs without significantly affecting levels of these mRNAs. A total of 180 of these mRNAs shared a common 20-nucleotide motif. Deletion of this motif from NEU3 mRNA eliminated the TGF-β1 upregulation of NEU3 translation, while insertion of this motif in 2 mRNAs insensitive to TGF-β1 caused TGF-β1 to upregulate their translation. RNA-binding proteins including DEAD box helicase 3, X-linked (DDX3), bind the RNA motif, and TGF-β1 regulates their protein levels and/or binding to the motif. We found that DDX3 was upregulated in the fibrotic lesions in patients with pulmonary fibrosis, and inhibiting DDX3 in fibroblasts reduced TGF-β1 upregulation of NEU3 levels. In the mouse bleomycin model of pulmonary fibrosis, injections of the DDX3 inhibitor RK-33 potentiated survival and reduced lung inflammation, fibrosis, and tissue levels of DDX3, TGF-β1, and NEU3. These results suggest that inhibiting an mRNA-binding protein that mediates TGF-β1 upregulation of translation can reduce pulmonary fibrosis.
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