Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditi ons. However, its role in atherosclerosis remains undefined. In this study, we admimistered vehicle o...Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditi ons. However, its role in atherosclerosis remains undefined. In this study, we admimistered vehicle or LECT2 to male Apoe^-/- mice fed a Western diet for 15 weeks. Atherosclerotic lesions were visualized and quantified with Oil-red O and hematoxylin staining. The mRNA expression levels of MCP-1, MMP-1, IL-8 IL-1β, and TNF-a were analyzed by quantitative real-time polymerase chain reaction. Serum TNF-a, IL-1β, IL-8, MCP-1, and MMP-1 concentrations were measured by en zyme-li nked immuno sorbent assay. CD68, CD31, and a-SMA, markers of macrophages, endothelial cells, and smooth muscle cells, respectively, were detected by immuno staining. Results showed that LECT2 reduced total cholesterol and low-density lipoprotein concentrations in serum and inhibited the development of atherosclerotic lesions, accompanied by reductions in inflammatory cytokines and lower MCP-1, MMP-1, TNF-a, IL-8, and IL-1β mRNA abundanee. Furthermore, LECT2 decreased CD68, but in creased cr SMA in atherosclerotic lesi ons, suggesting an in crease in smooth muscle cells and reduction in macrophages. In summary, LECT2 inhibited the development of atherosclerosis in mice, accompanied by reduced serum total cholesterol concentration and lower inflammatory responses.展开更多
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 ...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.展开更多
BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic st...BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery.AIM To investigate the infiltration changes of various immune cells in acute liver injury models over time,and to study the relationship between the changes in leukocyte cellderived chemotaxin 2(LECT2)and the infiltration of several immune cells.METHODS Carbon tetrachloride-and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively.The quantitative changes in various immune cells were monitored at different time points.Serum samples were collected,and liver tissues were harvested.Ly6G,CD161,CD4,CD8 and F4/80 staining were used to indicate neutrophils,NK/NKT cells,CD4^(+)T cells,CD8^(+)T cells and macrophages,respectively.Lect2-KO mice were used to detect the function of LECT2.RESULTS During the injury and repair process,different types of immune cells began to increase,reached their peaks and fell into decline at different time points.Furthermore,when the serum alanine transaminase(ALT)and aspartate transaminase(AST)indices reverted to normal levels 7 d after the injury,the infiltration of immune cells still existed even 14 d after the injury,showing an obvious lag effect.We found that the expression of LECT2 was upregulated in acute liver injury mouse models,and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice.Compared with wild-type mice,Lect2-KO mice had different immune cell infiltration.CONCLUSION The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair.LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.展开更多
基金supported by the Program for the National Natural Science Foundation of China(31772876)Ningbo Municipal Bureau of Science and Technology(2018A610389)+1 种基金Scientific Innovation Team Project of Ningbo(2015C110018)K.C.Wong Magna Fund in Ningbo University
文摘Leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional hepatokine, is involved in many pathological conditi ons. However, its role in atherosclerosis remains undefined. In this study, we admimistered vehicle or LECT2 to male Apoe^-/- mice fed a Western diet for 15 weeks. Atherosclerotic lesions were visualized and quantified with Oil-red O and hematoxylin staining. The mRNA expression levels of MCP-1, MMP-1, IL-8 IL-1β, and TNF-a were analyzed by quantitative real-time polymerase chain reaction. Serum TNF-a, IL-1β, IL-8, MCP-1, and MMP-1 concentrations were measured by en zyme-li nked immuno sorbent assay. CD68, CD31, and a-SMA, markers of macrophages, endothelial cells, and smooth muscle cells, respectively, were detected by immuno staining. Results showed that LECT2 reduced total cholesterol and low-density lipoprotein concentrations in serum and inhibited the development of atherosclerotic lesions, accompanied by reductions in inflammatory cytokines and lower MCP-1, MMP-1, TNF-a, IL-8, and IL-1β mRNA abundanee. Furthermore, LECT2 decreased CD68, but in creased cr SMA in atherosclerotic lesi ons, suggesting an in crease in smooth muscle cells and reduction in macrophages. In summary, LECT2 inhibited the development of atherosclerosis in mice, accompanied by reduced serum total cholesterol concentration and lower inflammatory responses.
文摘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.
基金Supported by the National Key R&D Program of ChinaNo. 2018YFA0108200 and No. 2018YFC1106400+5 种基金the National Natural Science Foundation of ChinaNo. 31972926, No. 32000607, No. 82270645 and No. 92068206Guangdong Basic and Applied Basic Research FoundationNo. 2020A1515111111 and No. 2019A1515110145China Postdoctoral Science FoundationNo. 2019M660205
文摘BACKGROUND Immune cells,including neutrophils,natural killer(NK)cells,T cells,NKT cells and macrophages,participate in the progression of acute liver injury and hepatic recovery.To date,there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery.AIM To investigate the infiltration changes of various immune cells in acute liver injury models over time,and to study the relationship between the changes in leukocyte cellderived chemotaxin 2(LECT2)and the infiltration of several immune cells.METHODS Carbon tetrachloride-and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively.The quantitative changes in various immune cells were monitored at different time points.Serum samples were collected,and liver tissues were harvested.Ly6G,CD161,CD4,CD8 and F4/80 staining were used to indicate neutrophils,NK/NKT cells,CD4^(+)T cells,CD8^(+)T cells and macrophages,respectively.Lect2-KO mice were used to detect the function of LECT2.RESULTS During the injury and repair process,different types of immune cells began to increase,reached their peaks and fell into decline at different time points.Furthermore,when the serum alanine transaminase(ALT)and aspartate transaminase(AST)indices reverted to normal levels 7 d after the injury,the infiltration of immune cells still existed even 14 d after the injury,showing an obvious lag effect.We found that the expression of LECT2 was upregulated in acute liver injury mouse models,and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice.Compared with wild-type mice,Lect2-KO mice had different immune cell infiltration.CONCLUSION The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair.LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.
