The protective function of galectin-9 in liver ischemia and reperfusion injury in mice.
The protective function of galectin-9 in liver ischemia and reperfusion injury in mice.
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DOI：
10.1002/lt.24159
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Uemoto S
中科院分区：
文献类型：
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作者：
Hirao H;Uchida Y;Kadono K;Tanaka H;Niki T;Yamauchi A;Hata K;Watanabe T;Terajima H;Uemoto S
Galectin-9（Gal-9）作为适应性和先天免疫的多方面参与者而受到关注。为了阐明Gal-9的作用，我们使用了野生型（WT）和Gal-9敲除（KO）小鼠以及重组半乳糖凝集素-9（reGal-9）蛋白的部分肝缺血/再灌注损伤（IRI）小鼠模型。我们发现，在小鼠肝脏的热IRI期间，Gal-9的表达在肝脏中内源性增强，特别是通过肝细胞和枯否细胞，这导致肝脏组织的大量破坏。Gal-9被释放到肝脏的细胞外空间，并在再灌注后1小时在血浆中达到最高水平。本研究通过使用Gal-9缺陷小鼠和稳定形式的reGal-9蛋白阐明了Gal-9信号在小鼠肝脏IRI中的新作用。在Gal-9缺乏的情况下，与WT相比，由于缺血/再灌注（IR）引起的肝损伤加重了严重程度。另一方面，外源性给予的reGal-9显著改善了肝细胞损伤。它减少了炎性细胞如T细胞、中性粒细胞和巨噬细胞的局部浸润，并减少了促炎细胞因子/趋化因子的表达;然后，它强烈抑制了肝细胞的凋亡。有趣的是，由于Gal-9 KO小鼠中IR引起的严重肝损伤通过给予reGal-9得到改善。总之，Gal-9参与改善了IR诱导的局部炎症和肝损伤，本研究表明Gal-9在维持肝脏稳态中具有重要作用。总之，靶向Gal-9代表了一种保护免受炎症（如肝脏IRI）的新方法。外源性Gal-9治疗将成为对抗先天免疫主导的肝组织损伤的新治疗策略。肝脏移植21：969 - 981，2015.© 2015 AASLD.
Galectin‐9 (Gal‐9) has gained attention as a multifaceted player in adaptive and innate immunity. To elucidate the role of Gal‐9, we used a mouse model of partial liver ischemia/reperfusion injury (IRI) with wild type (WT) and Gal‐9 knockout (KO) mice as well as a recombinant galectin‐9 (reGal‐9) protein. We found that the expression of Gal‐9 was enhanced endogenously in the liver especially by hepatocytes and Kupffer cells during warm IRI for a mouse liver, which causes massive destruction of liver tissue. Gal‐9 was released into the extracellular space in the liver and the highest levels in the plasma at 1 hour after reperfusion. The present study elucidates a novel role of Gal‐9 signaling in mouse liver IRI, by using Gal‐9–deficient mice and a stable form of reGal‐9 protein. In the circumstance of Gal‐9 absence, liver damage due to ischemia/reperfusion (IR) exacerbated the severity as compared with WT. On the other hand, exogenously administered reGal‐9 significantly ameliorated hepatocellular damage. It decreased the local infiltration of the inflammatory cells such as T cells, neutrophils, and macrophages, and it reduced the expression of proinflammatory cytokines/chemokines; then, it strongly suppressed the apoptosis of the liver cells. Interestingly, severe liver damage due to IR in Gal‐9 KO mice was improved by the administration of reGal‐9. In conclusion, Gal‐9 engagement ameliorated local inflammation and liver damage induced by IR, and the present study suggests a significant role of Gal‐9 in the maintenance of hepatic homeostasis. In conclusion, targeting Gal‐9 represents a novel approach to protect from inflammation such as liver IRI. Exogenous Gal‐9 treatment will be a new therapeutic strategy against innate immunity‐dominated liver tissue damage. Liver Transpl 21:969‐981, 2015. © 2015 AASLD.