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- Title
Tetramethylpyrazine ameliorates endotoxin-induced acute lung injury by relieving Golgi stress via the Nrf2/HO-1 signaling pathway.
- Authors
Li, Shaona; Xu, Yexiang; He, Simeng; Li, Xiangyun; Shi, Jia; Zhang, Bing; Zhu, Youzhuang; Li, Xiangkun; Wang, Yanting; Liu, Cuicui; Ma, Yang; Dong, Shuan; Yu, Jianbo
- Abstract
Purpose: Endotoxin-induced acute lung injury (ALI) is a severe disease caused by an imbalanced host response to infection. It is necessary to explore novel mechanisms for the treatment of endotoxin-induced ALI. In endotoxin-induced ALI, tetramethylpyrazine (TMP) provides protection through anti-inflammatory, anti-apoptosis, and anti-pyroptosis effects. However, the mechanism of action of TMP in endotoxin-induced ALI remains unclear. Here, we aimed to determine whether TMP can protect the lungs by inhibiting Golgi stress via the Nrf2/HO-1 pathway. Methods and results: Using lipopolysaccharide (LPS)-stimulated C57BL/6J mice and MLE12 alveolar epithelial cells, we observed that TMP pretreatment attenuated endotoxin-induced ALI. LPS + TMP group showed lesser lung pathological damage and a lower rate of apoptotic lung cells than LPS group. Moreover, LPS + TMP group also showed decreased levels of inflammatory factors and oxidative stress damage than LPS group (P < 0.05). Additionally, LPS + TMP group presented reduced Golgi stress by increasing the Golgi matrix protein 130 (GM130), Golgi apparatus Ca2+/Mn2+ ATPases (ATP2C1), and Golgin97 expression while decreasing the Golgi phosphoprotein 3 (GOLPH3) expression than LPS group (P < 0.05). Furthermore, TMP pretreatment promoted Nrf2 and HO-1 expression (P < 0.05). Nrf2-knockout mice or Nrf2 siRNA-transfected MLE12 cells were pretreated with TMP to explore how the Nrf2/HO-1 pathway affected TMP-mediated Golgi stress in endotoxin-induced ALI models. We observed that Nrf2 gene silencing partially reversed the alleviating effect of Golgi stress and the pulmonary protective effect of TMP. Conclusion: Our findings showed that TMP therapy reduced endotoxin-induced ALI by suppressing Golgi stress via the Nrf2/HO-1 signaling pathway in vivo and in vitro.
- Subjects
LUNG injuries; CELLULAR signal transduction; EXTRACELLULAR matrix proteins; GOLGI apparatus; GENE silencing
- Publication
BMC Pulmonary Medicine, 2023, Vol 23, Issue 1, p1
- ISSN
1471-2466
- Publication type
Article
- DOI
10.1186/s12890-023-02585-3