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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | 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. |
| Related Links | https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-023-02585-3.pdf |
| Ending Page | 18 |
| Page Count | 18 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14712466 |
| DOI | 10.1186/s12890-023-02585-3 |
| Journal | BMC Pulmonary Medicine |
| Issue Number | 1 |
| Volume Number | 23 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2023-08-07 |
| Access Restriction | Open |
| Subject Keyword | Pneumology Respiratory System Internal Medicine Intensive Critical Care Medicine Tetramethylpyrazine (TMP) Endotoxin Acute lung injury Golgi stress Nuclear factor erythroid-2 related factor 2 (Nrf2) Heme oxygenase-1 (HO-1) Pneumology/Respiratory System |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pulmonary and Respiratory Medicine |
| Journal Impact Factor | 2.6/2023 |
| 5-Year Journal Impact Factor | 3/2023 |
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