The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy.

IF 3.8 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-04-08 DOI:10.1038/s41598-025-95175-8

Yunping Bai, Xiaohong Yin, Qin Zhang, Xingjie Sang, Wenjing Wu, Dong Shao, Peng Zhao, Jiansheng Li

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引用次数: 0

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.

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JHF的有效复合相容性通过增强PINK1/ park2介导的有丝分裂抑制肺纤维化成纤维细胞活化。

通过建立BLM诱导的肺纤维化大鼠模型和转化生长因子-β（TGF-β）诱导的成纤维细胞活化模型，研究了ECC-JHF对肺纤维化和成纤维细胞活化的影响。此外，还在体内和体外探讨了ECC-JHF对Nrf2信号传导和有丝分裂的影响。在 PF 模型大鼠中，ECC-JHF 减轻了病理损伤，减少了胶原沉积，降低了丙二醛（MDA）和 P62 的水平，提高了总超氧化物歧化酶（T-SOD）的水平以及肺组织中 Nrf2、HO-1、PINK1、PARK2 和 LC3B 的表达。这些结果表明，ECC-JHF的抗PF机制可能与抑制氧化应激和增强有丝分裂有关。中等剂量的ECC-JHF和吡非尼酮在改善大鼠肺纤维化方面的作用相似。在 TGF-β 诱导的肺成纤维细胞活化中，ECC-JHF 通过下调纤维粘连蛋白、α-平滑肌肌动蛋白（α-SMA）和胶原 I 的水平抑制了成纤维细胞的活化。这导致 TOM20 和 LC3 的共定位增加，从而增强了线粒体自噬。应用 Nrf2 siRNA 和 Nrf2 抑制剂可明显减弱 ECC-JHF 对 Nrf2 信号转导、PINK1/PARK2 介导的有丝分裂和成纤维细胞活化的影响。ECC-JHF通过上调Nrf2和PINK1/PARK2介导的有丝分裂，抑制成纤维细胞活化，从而对肺纤维化产生保护作用，为肺纤维化的治疗提供了新的靶点和策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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