Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway
Abstract The inflammatory response of lung tissue and abnormal proliferation of pulmonary artery smooth muscle cells are involved in the pathogenesis of high-altitude pulmonary hypertension (HAPH). Halofuginone (HF), an active ingredient derivative of Chang Shan (Dichroa febrifuga Lour. [Hydrangeace...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-88258-z |
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| Summary: | Abstract The inflammatory response of lung tissue and abnormal proliferation of pulmonary artery smooth muscle cells are involved in the pathogenesis of high-altitude pulmonary hypertension (HAPH). Halofuginone (HF), an active ingredient derivative of Chang Shan (Dichroa febrifuga Lour. [Hydrangeaceae]), has antiproliferative, antihypertrophic, antifibrotic, and other effects, but its protective effects on HAPH remains unclear. In the present study, we evaluated the efficacy of HF on HAPH by establishing a 6000 m HAPH rat model. Male Sprague–Dawley rats were divided into normoxia, normoxia + halofuginone (1 mg/kg), hypoxia, and hypoxia + halofuginone (1 mg/kg) groups. The results showed that HF (1 mg/kg) could prevent hypoxia-induced hemodynamic abnormalities, right ventricular hypertrophy, and pulmonary vascular remodeling in rats. We further detected the expression levels of inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and proliferative/antiproliferative indicators proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 6 (CDK6), Cyclin D1, p21 in lung tissue, and found that HF could attenuate the lung tissue inflammatory response and proliferative response in HAPH rats. In addition, we also examined the expression levels of transforming growth factor-β1 (TGF-β1), Smad2/3 and p-Smad2/3 in lung tissue, and found that HF exerted therapeutic effects by inhibiting the TGF-β1/Smad signaling pathway. |
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| ISSN: | 2045-2322 |