Table 3.
Selected experimental and clinical findings associated with altered LCN2 expression in liver.
| Species | Model/disease | LCN2 detection method | LCN2 expression | Finding | References |
|---|---|---|---|---|---|
| Rat | Acute and chronic liver injury (CCl4, bile duct ligation) | IHC, WB, qRT-PCR | Elevated expression of LCN2 in hepatocytes after injury | LCN2 overexpression can indicate liver damage. Suggested as a biomarker of early hepatic injury | Borkham-Kamphorst et al., 2011 |
| Mice (WT and Lcn2−/−) | Acute liver injury (LPS, ConA, bile duct ligation) | ELISA, WB, qRT-PCR | Liver injury induced LCN2 upregulated expression | LCN2 is a trustworthy biomarker of hepatic damage and serves possible protective role in liver | Borkham-Kamphorst et al., 2013 |
| Lcn2-deficient mice | Hepatic inflammation (LPS) | NA | NA | LCN2 is an essential factor for regulation of inflammatory process manifestations during liver injury | Labbus et al., 2013 |
| Human | Hepatic cirrhosis | ELISA | Increased expression in patients | Urine LCN2 is a prognosis marker of cirrhosis | Ariza et al., 2016 |
| Rat | Chronic rejection | Mass spectrometry | LCN2 elevation in the chronic rejection group | LCN2 potential prognostic markers for predicting chronic rejection after liver transplantation | Wei et al., 2015 |
| Human | Chronic HCV-induced fibrosis | ELISA, WB, Gelatin zymography | Urine LCN2 levels higher in patients with fibrosis/cirrhosis in the same line as MMP-9/MMP-2 ratio | Urinary LCN2 is a novel marker of hepatic fibrosis by reflecting urine MMP-9 activity in chronic hepatitis C | Kim et al., 2010 |
| Human | Acute liver failure and chronic liver failure | ELISA | Baseline LCN-2 serum concentrations were significantly increased among acute liver failure patients as compared with chronic hepatic failure | LCN2 useful to discern acute from chronic hepatic failure and to monitor severity of the disease | Roth et al., 2013 |
| Human | Chinese patients with NAFLD | ELISA | Circulating LCN2 elevated in patients compared healthy controls | Serum LCN2, correlates with inflammation and insulin resistance, and is correlated with disease progression | Ye et al., 2014 |
| Human | Obese women with NAFLD | ELISA | Liver LCN2 protein and gene expression were higher in NAFLD than obese women without NAFLD | LCN2 related to NAFLD and liver damage | Auguet et al., 2013 |
| Human | NAFLD patients | ELISA | Urinary LCN2 levels correlated with body mass index, glucose, and insulin levels in patients with steatosis; LCN2 levels correlated also with fibrosis stage and cirrhosis | LCN2 has a novel association between urinary levels and hepatocellular injury in these patients | Tekkesin et al., 2012 |
| Mice (WT and Lcn2−/−) | High fat diet induced-NAFLD | WB | The molecular disruption of Lcn2 in mice resulted in significantly potentiated diet-induced obesity, dyslipidemia, fatty liver disease, and insulin resistance | LCN2 contributes in regulation of lipid metabolism and insulin resistance | Guo et al., 2010 |
| Mice (WT and Lcn2−/−) | High fat diet induced-obesity | NA | LCN2 supports function of PPAR-γ ligands | LCN2 regulates hepatic lipogenesis by affecting PPAR- γ expression | Jin et al., 2011 |
| Rats | High fructose diet-induced NAFLD | WB, qRT-PCR, IF, ELISA | Overexpression of LCN2 in NAFLD mice | LCN2 to be correlated to inflammation, mitochondrial malfunction, oxidative stress and liver protective qualities | Alwahsh et al., 2014 |
| Mice (WT and Lcn2−/−) | MCD diet-induced-NASH | WB, qRT-PCR, IF | Overexpression of LCN2 in NASH mice; LCN2 regulates PLIN5 expression in hepatocytes | LCN2 regulates liver lipid homeostasis by partially regulating PLIN5 expression | Asimakopoulou et al., 2014 |
| Mice | Genetically induced NASH with fatty liver Shionogi mice | qRT-PCR, IHC | NASH mice presented higher LCN2 expression | LCN2 has a key role in NASH development | Semba et al., 2013 |
| Human | Alcoholic fatty liver disease (AFLD) patients | ELISA | Increased hepatic LCN2 in AFLD patients compared to patients with alcoholic cirrhosis or simple steatosis | LCN2 drives ethanol-induced neutrophilic inflammation and participates in the development of AFLD; pharmacological neutralization of LCN2 is a potential treatment | Wieser et al., 2016 |
| Mice (WT and Lcn2−/−) | MCD diet-induced-NASH | WB, qRT-PCR, IF | LCN2 elevated levels after MCD diet for 4 weeks induced intense leukocyte recruitment | LCN2 has an hepatoprotective role as it is required in neutrophil trafficking to liver | Asimakopoulou et al., 2016 |
| Human | Patients who underwent curative resection of HCC | IHC | The expression levels of LCN2 and its receptor were both up-regulated in HCC tissues; high expression correlated with shorter overall survival | Expression of LCN2 and its receptor might serve in HCC prognosis and therapy | Zhang et al., 2012 |
| Human | HCC patients | ELISA | Increased LCN2 expression in patients with HCV and HCC | LCN2 can be used as a future diagnostic marker with better sensitivity and specificity than MMP-9 for the progression of HCC | El Moety et al., 2013 |
| Mice (WT and Lcn2−/−) | Bacterial infection or partial hepatectomy | ELISA | Lcn2-deficient mice demonstrated increased susceptibility to infection and reduced liver regeneration after hepatectomy | Hepatocytes are the major cell type responsible for LCN2 production after bacterial infection and hepatectomy; hepatocytic-derived LCN2 has important hepatoprotective roles in those conditions | Xu et al., 2015 |
ConA, Concanavalin A; ELISA, Enzyme-linked immunosorbent assay; HCC, hepatocellular carcinoma; IF, immunofluoresence; IHC, immunohistochemistry; LPS, lipopolysaccharide; MCD, Methionine-choline-deficient diet; NASH, non-alcoholic steatohepatitis; PLIN5, Perilipin 5; PPAR- γ, Peroxisome proliferator-activated receptor-γ; qRT-PCR, quantitative real time polymerase chain reaction; WB, Western blot.