Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia–reperfusion injury

Q2 Medicine

Liver Research Pub Date : 2024-09-01 DOI:10.1016/j.livres.2024.09.004

Meng-Qi Dong , Yuan Xie , Zhi-Liang Tang , Xue-Wen Zhao , Fu-Zhen Lin , Guang-Yu Zhang , Zhi-Hao Huang , Zhi-Min Liu , Yuan Lin , Feng-Yong Liu , Wei-Jie Zhou

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Abstract

Background and aim

Hepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors.

Materials and methods

This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed.

Results

Serum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential.

Conclusions

Elevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

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白细胞细胞衍生趋化因子 2 (LECT2) 调节肝脏缺血再灌注损伤

背景和目的肝脏缺血再灌注损伤（IRI）是肝移植、创伤、低血容量休克和肝切除术中的一个重大挑战，目前有效的干预措施有限。本研究旨在探讨白细胞细胞衍生趋化因子2（LECT2）在肝脏IRI中的作用，并评估通过腺相关病毒（AAV）载体递送的Lect2-短发夹RNA（shRNA）的治疗潜力。研究使用了 Lect2- 基因剔除小鼠和 C57BL/6J 小鼠。通过夹闭肝梗诱导肝脏IRI。治疗包括重组人LECT2（rLECT2）和AAV-Lect2-shRNA。测量了LECT2的表达水平和血清生物标志物，包括丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、肌酐和血尿素氮（BUN）。结果肝脏IRI期间血清和肝脏LECT2水平升高。再灌注后血清 LECT2 蛋白和 mRNA 水平升高。Lect2 基因敲除小鼠的体重减轻、肝坏死和血清 ALT、AST、肌酐和 BUN 水平降低。AAV-LECT2-shRNA治疗显著减轻了体重下降、肝坏死和血清生物标志物（谷丙转氨酶、谷草转氨酶、肌酐和尿素氮），显示出治疗潜力。基因敲除或 shRNA 介导的 Lect2 基因敲除可减轻肝损伤，显示了其治疗潜力。AAV介导的Lect2-shRNA递送减轻了肝脏IRI，为提高肝脏相关手术或外伤患者的临床疗效提供了一种潜在的新治疗策略。

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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