ArticleArthritis research & therapy2022
The compound LG283 inhibits bleomycin-induced skin fibrosis via antagonizing TGF-β signaling.
Article in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 16 citations in OpenAlex.
- Development of Local Bleomycin-Induced Hindlimb Model Recapitulating Skin Fibrosis and Vasculopathy of Systemic Sclerosis.Archives of plastic surgery · 2026Article
- Network pharmacology and in vivo experimental analysis for validating the antifibrotic potential of Punica granatum leaves against skin scleroderma: the role of oxidative stress, inflammation and TGF-β1/Snail 1/p-Smad 3 signaling pathway.Inflammopharmacology · 2026Article
- SUN2 mediates epigenetic remodeling to drive mechanotransduction during skin fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Epithelial-mesenchymal transition in cutaneous fibrosis disease: from mechanisms to therapy.Frontiers in immunology · 2026Review
- Targeting inflammation, fibrosis, and vascular dysfunction in systemic sclerosis: the role of diet and complementary and alternative medicine.Current opinion in rheumatology · 2025Review
- Advances in the research and application of stem cell therapies for idiopathic pulmonary fibrosis.American journal of clinical and experimental immunology · 2025Review
- Anti-CX3CL1 (fractalkine) monoclonal antibody attenuates lung and skin fibrosis in sclerodermatous graft-versus-host disease mouse model.Arthritis research & therapy · 2024Article
- Mesenchymal stem cell-derived extracellular vesicles in systemic sclerosis: role and therapeutic directions.Frontiers in cell and developmental biology · 2024Review
- Antioxidant therapy against TGF-β/SMAD pathway involved in organ fibrosis.Journal of cellular and molecular medicine · 2024Review
- Biomarkers in Systemic Sclerosis: An Overview.Current issues in molecular biology · 2023Review
- Involvement of Epithelial-Mesenchymal Transition (EMT) in Autoimmune Diseases.International journal of molecular sciences · 2023Review
- Novel Therapeutic Strategies in the Treatment of Systemic Sclerosis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes.Nutrients · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSystemic sclerosis (SSc) is a collagen disease that exhibits intractable fibrosis and vascular injury of the skin and internal organs. Transforming growth factor-β (TGF-β)/Smad signaling plays a central role in extracellular matrix (ECM) production by α-SMA-positive myofibroblasts. Myofibroblasts may be partially derived from various precursor cells in addition to resident fibroblasts. Recently, our high-throughput in vitro screening discovered a small compound, LG283, that may disrupt the differentiation of epithelial cells into myofibroblasts. This compound was originally generated as a curcumin derivative.
methodsIn this study, we investigated the effect of LG283 on inhibiting fibrosis and its mechanism. The action of LG283 on TGF-β-dependent fibrogenic activity and epithelial-mesenchymal transition (EMT) was analyzed in vitro. The effects of LG283 were also examined in a bleomycin-induced skin fibrosis mouse model.
resultsLG283 suppressed TGF-β-induced expression of ECM, α-SMA, and transcription factors Snail 1 and 2, and Smad3 phosphorylation in cultured human dermal fibroblasts. LG283 was also found to block EMT induction in cultured human epithelial cells. During these processes, Smad3 phosphorylation and/or expression of Snail 1 and 2 were inhibited by LG283 treatment. In the bleomycin-induced skin fibrosis model, oral administration of LG283 efficiently protected against the development of fibrosis and decrease of capillary vessels without significantly affecting cell infiltration or cytokine concentrations in the skin. No apparent adverse effects of LG283 were found. LG283 treatment remarkably inhibited the enhanced expression of α-SMA and phosphorylated Smad3, as well as those of Snail 1 and 2, in the bleomycin-injected skin.
conclusionsThe LG283 compound exhibits antagonistic activity on fibrosis and vascular injury through inhibition of TGF-β/Smad/Snail mesenchymal transition pathways and thus, may be a candidate therapeutic for the treatment of SSc. Although the involvement of EMT in the pathogenesis of SSc remains unclear, the screening of EMT regulatory compounds may be an attractive approach for SSc therapy.
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