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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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88258-z |
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| author | Jiangtao Wang Lina Guan Jian Yu Bohua Ma Huihua Shen Guozhu Xing Yawei Xu Qiufang Li Juan Liu Qin Xu Wenhui Shi Jia He Yixuan Huang Dongfeng Yin Wu Li Rui Wang |
| author_facet | Jiangtao Wang Lina Guan Jian Yu Bohua Ma Huihua Shen Guozhu Xing Yawei Xu Qiufang Li Juan Liu Qin Xu Wenhui Shi Jia He Yixuan Huang Dongfeng Yin Wu Li Rui Wang |
| author_sort | Jiangtao Wang |
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| description | 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. |
| format | Article |
| id | doaj-art-67fa19fe74044dd9a8c21219b5878094 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-67fa19fe74044dd9a8c21219b58780942025-02-02T12:17:46ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-88258-zHalofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathwayJiangtao Wang0Lina Guan1Jian Yu2Bohua Ma3Huihua Shen4Guozhu Xing5Yawei Xu6Qiufang Li7Juan Liu8Qin Xu9Wenhui Shi10Jia He11Yixuan Huang12Dongfeng Yin13Wu Li14Rui Wang15General Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandTumor Hospital of Xinjiang Medical UniversityDepartment of Pharmacy, Qingyang People’s HospitalGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandXinjiang Key Laboratory of Special Environmental MedicineXinjiang Key Laboratory of Special Environmental MedicineGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandGeneral Hospital of Xinjiang Military CommandAbstract 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.https://doi.org/10.1038/s41598-025-88258-zHypoxiaPulmonary hypertensionRemodelingInflammationProliferationTGF-β1/Smad signaling pathway |
| spellingShingle | Jiangtao Wang Lina Guan Jian Yu Bohua Ma Huihua Shen Guozhu Xing Yawei Xu Qiufang Li Juan Liu Qin Xu Wenhui Shi Jia He Yixuan Huang Dongfeng Yin Wu Li Rui Wang Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway Scientific Reports Hypoxia Pulmonary hypertension Remodeling Inflammation Proliferation TGF-β1/Smad signaling pathway |
| title | Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway |
| title_full | Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway |
| title_fullStr | Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway |
| title_full_unstemmed | Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway |
| title_short | Halofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway |
| title_sort | halofuginone prevents inflammation and proliferation of high altitude pulmonary hypertension by inhibiting the tgf β1 smad signaling pathway |
| topic | Hypoxia Pulmonary hypertension Remodeling Inflammation Proliferation TGF-β1/Smad signaling pathway |
| url | https://doi.org/10.1038/s41598-025-88258-z |
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