Leukocyte cell-derived chemotaxin 2(LECT2)regulates liver ischemia-reperfusion injury
10.1016/j.livres.2024.09.004
- Author:
Dong MENG-QI
1
;
Xie YUAN
;
Tang ZHI-LIANG
;
Zhao XUE-WEN
;
Lin FU-ZHEN
;
Zhang GUANG-YU
;
Huang ZHI-HAO
;
Liu ZHI-MIN
;
Lin YUAN
;
Liu FENG-YONG
;
Zhou WEI-JIE
Author Information
1. State Key Laboratory of Organ Failure Research
- Keywords:
Hepatic ischemia-reperfusion injury(IRI);
Leukocyte cell-derived chemotaxin 2(LECT2);
Adeno-associated virus(AAV)
- From:
Liver Research
2024;8(3):165-171
- CountryChina
- Language:Chinese
-
Abstract:
Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,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 under-going 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 thera-peutic 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.
