The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy
Abstract This work aimed to elucidate the anti-PF mechanism of ECC-JHF.The effects of ECC-JHF on lung fibrosis and fibroblast activation were investigated by establishing a BLM-induced PF rat model and a transforming growth factor-beta (TGF-β)-induced fibroblast activation model. Furthermore, the ef...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-95175-8 |
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| author | Yunping Bai Xiaohong Yin Qin Zhang Xingjie Sang Wenjing Wu Dong Shao Peng Zhao Jiansheng Li |
| author_facet | Yunping Bai Xiaohong Yin Qin Zhang Xingjie Sang Wenjing Wu Dong Shao Peng Zhao Jiansheng Li |
| author_sort | Yunping Bai |
| collection | DOAJ |
| description | Abstract This work aimed to elucidate the anti-PF mechanism of ECC-JHF.The effects of ECC-JHF on lung fibrosis and fibroblast activation were investigated by establishing a BLM-induced PF rat model and a transforming growth factor-beta (TGF-β)-induced fibroblast activation model. Furthermore, the effects of ECC-JHF on Nrf2 signaling and mitophagy were explored both in vivo and in vitro. In the PF model rats, ECC-JHF mitigated pathological damage, reduced collagen deposition, decreased levels of malondialdehyde (MDA) and P62, and increased levels of total superoxide dismutase (T-SOD) as well as the expression of Nrf2, HO-1, PINK1, PARK2, and LC3B in lung tissues. These results suggest that the anti-PF mechanism of ECC-JHF may be associated with the inhibition of oxidative stress and the enhancement of mitophagy. The medium dose of ECC-JHF and pirfenidone were similar in improving pulmonary fibrosis in rats. In the TGF-β-induced lung fibroblast activation, ECC-JHF inhibited fibroblast activation by downregulating the levels of fibronectin, alpha-smooth muscle actin (α-SMA), and collagen I. Additionally, ECC-JHF upregulated the level of Nrf2 and its target proteins, including HO-1 and NQO1, as well as mitophagy-related proteins PINK1, PARK2, and LC3B. This led to an increase in the co-localization of TOM20 and LC3, thereby enhancing mitochondrial autophagy. The application of Nrf2 siRNA and Nrf2 inhibitors significantly diminished the effects of ECC-JHF on Nrf2 signaling, PINK1/PARK2-mediated mitophagy, and fibroblast activation. ECC-JHF exerts a protective effect against PF by suppressing fibroblast activation through the upregulation of Nrf2 and PINK1/PARK2-mediated mitophagy, it provides a new target and strategy for the treatment of pulmonary fibrosis. |
| format | Article |
| id | doaj-art-863569feee6b4e85ab5d2a60cee7f676 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-863569feee6b4e85ab5d2a60cee7f6762025-08-20T02:17:13ZengNature PortfolioScientific Reports2045-23222025-04-0115111410.1038/s41598-025-95175-8The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagyYunping Bai0Xiaohong Yin1Qin Zhang2Xingjie Sang3Wenjing Wu4Dong Shao5Peng Zhao6Jiansheng Li7Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineHenan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese MedicineAbstract This work aimed to elucidate the anti-PF mechanism of ECC-JHF.The effects of ECC-JHF on lung fibrosis and fibroblast activation were investigated by establishing a BLM-induced PF rat model and a transforming growth factor-beta (TGF-β)-induced fibroblast activation model. Furthermore, the effects of ECC-JHF on Nrf2 signaling and mitophagy were explored both in vivo and in vitro. In the PF model rats, ECC-JHF mitigated pathological damage, reduced collagen deposition, decreased levels of malondialdehyde (MDA) and P62, and increased levels of total superoxide dismutase (T-SOD) as well as the expression of Nrf2, HO-1, PINK1, PARK2, and LC3B in lung tissues. These results suggest that the anti-PF mechanism of ECC-JHF may be associated with the inhibition of oxidative stress and the enhancement of mitophagy. The medium dose of ECC-JHF and pirfenidone were similar in improving pulmonary fibrosis in rats. In the TGF-β-induced lung fibroblast activation, ECC-JHF inhibited fibroblast activation by downregulating the levels of fibronectin, alpha-smooth muscle actin (α-SMA), and collagen I. Additionally, ECC-JHF upregulated the level of Nrf2 and its target proteins, including HO-1 and NQO1, as well as mitophagy-related proteins PINK1, PARK2, and LC3B. This led to an increase in the co-localization of TOM20 and LC3, thereby enhancing mitochondrial autophagy. The application of Nrf2 siRNA and Nrf2 inhibitors significantly diminished the effects of ECC-JHF on Nrf2 signaling, PINK1/PARK2-mediated mitophagy, and fibroblast activation. ECC-JHF exerts a protective effect against PF by suppressing fibroblast activation through the upregulation of Nrf2 and PINK1/PARK2-mediated mitophagy, it provides a new target and strategy for the treatment of pulmonary fibrosis.https://doi.org/10.1038/s41598-025-95175-8Pulmonary fibrosisEffective-compound combinationFibroblasts activationNrf2Mitophagy |
| spellingShingle | Yunping Bai Xiaohong Yin Qin Zhang Xingjie Sang Wenjing Wu Dong Shao Peng Zhao Jiansheng Li The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy Scientific Reports Pulmonary fibrosis Effective-compound combination Fibroblasts activation Nrf2 Mitophagy |
| title | The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy |
| title_full | The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy |
| title_fullStr | The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy |
| title_full_unstemmed | The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy |
| title_short | The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy |
| title_sort | effective compound compatibility of jhf inhibits fibroblast activation in pulmonary fibrosis by enhancing pink1 park2 mediated mitophagy |
| topic | Pulmonary fibrosis Effective-compound combination Fibroblasts activation Nrf2 Mitophagy |
| url | https://doi.org/10.1038/s41598-025-95175-8 |
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