Dokument: Antifibrotic effects of specific targeting of the 5‐hydroxytryptamine 2B receptor (5‐HT2BR) in murine models and ex vivo models of scleroderma skin
| Titel: | Antifibrotic effects of specific targeting of the 5‐hydroxytryptamine 2B receptor (5‐HT2BR) in murine models and ex vivo models of scleroderma skin | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=70722 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250911-094714-0 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Trinh, Minh Thuong [Autor] Tran, Manh Cuong [Autor] Györfi, Andrea-Hermina [Autor] Dickel, Nicholas [Autor] Liebel, Christoph [Autor] Zhou, Xiang [Autor] Wang, Jiucun [Autor] Kunz, Meik [Autor] Arozenius, Helena [Autor] Pettersson, Lars [Autor] | |||||||
| Dateien: |
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| Beschreibung: | Objective
Systemic sclerosis (SSc) is a connective tissue disease with fibrotic remodeling of the skin and various internal organs. SSc is associated with the highest case-specific mortality of all rheumatic autoimmune diseases with limited antifibrotic treatment options. Here, we evaluated the therapeutic effects of the highly selective 5-hydroxytryptamine 2B receptor (5-HT 2B R) inhibitor AM1476. Methods The antifibrotic effects of AM1476 were evaluated in the mouse models of bleomycin-induced pulmonary fibrosis in Tsk-1 mice and in mice with sclerodermatous chronic graft-versus-host disease. For further validation, the antifibrotic effects of AM1476 were analyzed in precision cut skin (PCS) slices from patients with SSc. Results AM1476 demonstrated high selectivity for 5-HT 2B R over more than 200 other receptors, including other 5-HT receptors in vitro. AM1476 reduced accumulation of hydroxyproline and fibrotic tissue remodeling of skin and/or lungs in all three mouse models at well-tolerated doses with a comparable efficacy to that of nintedanib. In PCS of SSc skin, treatment with AM1476 reduced the expression of SSc-specific signature genes. AM1476 demonstrated more pronounced regulation of terms related to fibroblast activation and fibrotic remodeling than mycophenolate mofetil. Conclusion We describe AM1476 as a highly selective inhibitor of 5-HT 2B R. Treatment with AM1476 ameliorated fibrosis in three mouse models of SSc and normalized the expression of fibrosis-related genes directly in SSc skin. Because AM1476 also demonstrated good tolerability in a phase 1 trial, further clinical trials with AM1476 are currently in the planning stage. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Trinh, M. T., Tran, M. C., Györfi, A.-H., Dickel, N., Liebel, C., Zhou, X., Wang, J., Kunz, M., Arozenius, H., Pettersson, L., Lindgren, S., Wenglén, C., & Distler, J. (2025). Antifibrotic effects of specific targeting of the 5‐hydroxytryptamine 2B receptor (5‐HT2BR) in murine models and ex vivo models of scleroderma skin. Arthritis & Rheumatology, 77(8), 1063–1076. https://doi.org/10.1002/art.43151 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 11.09.2025 | |||||||
| Dateien geändert am: | 11.09.2025 |
