Lipocalin 2 (LCN2) Expression in Hepatic Malfunction and Therapy

Abstract

Lipocalin 2 (LCN2) is a secreted protein that belongs to the Lipocalins, a group of transporters of small lipophilic molecules such as steroids, lipopolysaccharides, iron, and fatty acids in circulation. Two decades after its discovery and after a high variety of published findings, LCN2's altered expression has been assigned to critical roles in several pathological organ conditions, including liver injury and steatosis, renal damage, brain injury, cardiomyopathies, muscle-skeletal disorders, lung infection, and cancer in several organs. The significance of this 25-kDa lipocalin molecule has been impressively increased during the last years. Data from several studies indicate the role of LCN2 in physiological conditions as well as in response to cellular stress and injury. LCN2 in the liver shows a protective role in acute and chronic injury models where its expression is highly elevated. Moreover, LCN2 expression is being considered as a potential strong biomarker for pathological conditions, including rheumatic diseases, cancer in human organs, hepatic steatosis, hepatic damage, and inflammation. In this review, we summarize experimental and clinical findings linking LCN2 to the pathogenesis of liver disease.

Hepatocytes and neutrophils cooperatively suppress bacterial infection by differentially regulating lipocalin‐2 and neutrophil extracellular traps

“…However, whether and how LCN2 regulates inflammation during bacterial infection and during chronic sterile inflammation in liver disease remain obscure. As mentioned in the introduction, the role of LCN2 in regulating inflammation has been controversial in various types of diseases, including liver disorders . In the acute bacterial infection model used in the current study, genetic deletion of the Lcn2 gene in hepatocytes or myeloid cells, or both, had little impact on inflammatory responses, suggesting that LCN2 may not have an important role in regulating inflammation in acute bacterial infection; however, we cannot rule out that LCN2 may play a role in the control of inflammatory response during chronic bacterial infection.…”

The role of lipocalin-2 in age-related macular degeneration (AMD)

“…The closure of the sheet to form the lipocalin β-barrel breaks the symmetry of its elliptical cross-section, distinguishing between its two foci and suggesting a sidedness to the barrel also apparent in the location of the marked SCRs. Reproduced with permission from Flower et al (1996) [2] are different names for human LCN-2 including neutrophil gelatinase-associated lipocalin (NGAL), human neutrophil lipocalin (HNL), uterocalin, 25 kDa α2-microglobulinrelated protein, oncogene 24p3 protein (24p3), siderocalin, α2μ-globulin, neu-related lipocalin (NRL) in rat, and 24 kDa superinducible protein (Sip24) in mouse [16][17][18][19]. These names were chosen based either on the observed role of LCN-2 or the specific tissue in which its expression was first noticed [16].…”

“…Reproduced with permission from Flower et al (1996) [2] are different names for human LCN-2 including neutrophil gelatinase-associated lipocalin (NGAL), human neutrophil lipocalin (HNL), uterocalin, 25 kDa α2-microglobulinrelated protein, oncogene 24p3 protein (24p3), siderocalin, α2μ-globulin, neu-related lipocalin (NRL) in rat, and 24 kDa superinducible protein (Sip24) in mouse [16][17][18][19]. These names were chosen based either on the observed role of LCN-2 or the specific tissue in which its expression was first noticed [16]. There are two different forms of LCN-2, one form is monomeric with a 10-min half-life and the other is dimeric with a 20-min half-life [20].…”

“…Higher levels of LCN-2 are found in tissues that are constantly exposed to microorganisms including prostate, salivary gland, uterus, stomach, colon, and appendix. Moreover, in some tissues such as kidney and liver, the level of LCN-2 is reduced during senescence [16,22]. Although LCN-2 expression begins in the embryo [23], it has been demonstrated that it is strongly activated in inflamed organs, where it is expressed either by different resident cells or by circulating immune cells which enter the tissue [16,24,25].…”

“…Moreover, in some tissues such as kidney and liver, the level of LCN-2 is reduced during senescence [16,22]. Although LCN-2 expression begins in the embryo [23], it has been demonstrated that it is strongly activated in inflamed organs, where it is expressed either by different resident cells or by circulating immune cells which enter the tissue [16,24,25]. A low level of LCN-2 is detectable in bodily fluids, however, under pathological conditions, this level may increase [16,26].…”