Galectin-1 ameliorates lipopolysaccharide-induced acute lung injury via AMPK-Nrf2 pathway in mice
Galectin-1 ameliorates lipopolysaccharide-induced acute lung injury via AMPK-Nrf2 pathway in mice
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DOI：
10.1016/j.freeradbiomed.2019.11.011
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发表时间：
2020-01-01
影响因子：
7.4
通讯作者：
Tang, Si-Yuan
中科院分区：
文献类型：
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作者：
Huang, Xiao-Ting;Liu, Wei;Tang, Si-Yuan
炎症和氧化应激促进急性肺损伤（ALI）的进展。半乳糖凝集素-1（Galectin-1）在肾缺血-再灌注损伤、关节炎、葡萄膜炎和肝炎中具有重要的抗炎特性。然而，Gal-1是否可以保护对ALI仍然很不清楚。本研究旨在探讨Gal-1对脂多糖（LPS）诱导的急性肺损伤的保护作用及其机制。因此，我们发现Gal-1预处理减轻了LPS诱导的肺组织损伤，肺功能恢复，保护免受促炎细胞因子和氧化应激的产生。我们还证实了Gal-1对LPS攻击小鼠存活率的治疗潜力。体外研究表明，外源性Gal-1通过下调LPS攻击的原代巨噬细胞中促炎细胞因子释放和氧化应激来发挥保护作用。此外，Gal-1抑制ALI小鼠和LPS处理的原代巨噬细胞中TXNIP-NLRP 3炎性体活化，部分是通过直接结合NLRP 3蛋白。Gal-1通过激活Nrf-2来减轻LPS诱导的肺损伤，这可能与AMPK磷酸化有关。总的来说，我们的实验结果首先提供了支持，Gal-1通过抑制炎症反应和氧化应激有效地保护LPS诱导的ALI，这在很大程度上依赖于通过AMPK磷酸化上调Nrf 2通路。这些结果表明，Gal-1可能是一个有价值的治疗候选人在治疗ALI。
Inflammation and oxidative stress contribute to the progression of acute lung injury (ALI). Galectin-1 (Gal-1) has important anti-inflammatory properties in renal ischemia-reperfusion injury, arthritis, uveitis, and hepatitis. However, whether Gal-1 could protect against ALI is still poorly elucidated. The current study aimed to investigate the protective effects of Gal-1 against lipopolysaccharide (LPS)-induced ALI and the underlying mechanisms. Accordingly, we found that pretreatment with Gal-1 attenuated the lung tissue injury induced by LPS, with the recovery of lung function, protecting against the production of pro-inflammatory cytokines and oxidative stress. We also confirmed the therapeutic potential of Gal-1 on the survival rate of LPS-challenged mice. In vitro studies demonstrated the protective effects of exogenous Gal-1 through downregulating pro-inflammatory cytokines release and oxidative stress in primary macrophages challenged by LPS. In addition, Gal-1 suppressed TXNIP-NLRP3 inflammasome activation in ALI mice and LPS-treated primary macrophages partly through directly binding to the NLRP3 protein. Gal-1 alleviated LPS-induced lung injury via activation of Nrf-2, which may be associated with AMPK phosphorylation. Collectively, our experimental results firstly provided the support that Gal-1 effectively protected against LPS-induced ALI via suppression of inflammation response and oxidative stress, which were largely dependent on the upregulation of the Nrf2 pathway via phosphorylation of AMPK. These results suggest that Gal-1 could be a valuable therapeutic candidate in the treatment of ALI.