Protective effects of lipocalin-2 (LCN2) in acute liver injury suggest a novel function in liver homeostasis

Borkham-Kamphorst, Erawan; Leur, Eddy Van de; Zimmermann, Henning W.; Karlmark, Karlin Raja; Tihaa, Lidia; Haas, Ute; Tacke, Frank; Berger, Thorsten; Mak, Tak W.; Weiskirchen, Ralf

doi:10.1016/j.bbadis.2013.01.014

Cited by 118 publications

(134 citation statements)

References 43 publications

Supporting

Mentioning

124

Contrasting

Order By: Relevance

“…In addition, the expression of vimentin that indicates increasing amounts of myofibroblasts or fibroblasts is increased after setting of the BDL surgery 20 . The concomitance of inflammation in injured livers are further reflected by increased expression of Lipocalin 2 (LCN2) that is strongly induced during acute and chronic liver injury and evolves hepato-protective effects during acute liver injury 21,22 .…”

Section: Representative Resultsmentioning

confidence: 99%

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Tag

Sauer-Lehnen

Weiskirchen

et al. 2015

JoVE

Self Cite

221

210

View full text Add to dashboard Cite

In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well as to excrete bilirubin and other metabolic products. In the liver, the experimental obstruction of the extrahepatic biliary system initiates a complex cascade of pathological events that leads to cholestasis and inflammation resulting in a strong fibrotic reaction originating from the periportal fields. Therefore, surgical ligation of the common bile duct has become the most commonly used model to induce obstructive cholestatic injury in rodents and to study the molecular and cellular events that underlie these pathophysiological mechanisms induced by inappropriate bile flow. In recent years, different surgical techniques have been described that either allow reconnection or reanastomosis after bile duct ligation (BDL), e.g., partial BDL, or other microsurgical methods for specific research questions. However, the most frequently used model is the complete obstruction of the common bile duct that induces a strong fibrotic response after 21 to 28 days. The mortality rate can be high due to infectious complications or technical inaccuracies. Here we provide a detailed surgical procedure for the BDL model in mice that induce a highly reproducible fibrotic response in accordance to the 3R rule for animal welfare postulated by Russel and Burch in 1959.

show abstract

Section: Representative Resultsmentioning

confidence: 99%

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Tag

Sauer-Lehnen

Weiskirchen

et al. 2015

JoVE

Self Cite

221

210

View full text Add to dashboard Cite

show abstract

“…2 The presented data corroborate our previous findings that injury-induced up-regulation of hepatic LCN2 has a significant hepatoprotective effect in acute liver injury and that hepatocytes are the major source for hepatic LCN2. 3,4 Furthermore, these data suggest that LCN2 might act as an intrinsic "help-me" sensor that, upon injury, develops an activity necessary to recruit inflammatory cells. In line with this assumption, we observed that lcn2-deficient mice showed a significant lower recruitment of neutrophils and leukocytes, compared to wild-type (WT) animals, when fed with a methionine-choline-deficient (MCD) diet that induces hepatic inflammation and injury (Fig.…”

mentioning

confidence: 99%

Lipocalin‐2 (NGAL/LCN2), a “help‐me” signal in organ inflammation

et al. 2015

Self Cite

View full text Add to dashboard Cite

“…Other immune modifiers may be drivers for the fibrosis observed in the NGN group. Notably, pretreatment with NVP modified the inflammatory response, dampening the initial M1 inflammatory response to galactosamine presumably via upregulation of lipocalin 2 (Borkham-Kamphorst et al 2013), which pushes macrophage polarization toward the M2 pathway and slightly elevates the apoptotic response. Lipocalin 2 is a soluble secreted protein that binds iron and is protective against hepatic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Drug-induced Liver Fibrosis

et al. 2016

View full text Add to dashboard Cite

Nevirapine (NVP) is associated with hepatotoxicity in 1-5% of patients. In rodent studies, NVP has been shown to cause hepatic enzyme induction, centrilobular hypertrophy, and skin rash in various rat strains but not liver toxicity. In an effort to understand whether NVP is metabolized differently in a transiently inflamed liver and whether a heightened immune response alters NVPinduced hepatic responses, female brown Norway rats were dosed with either vehicle or NVP alone (75 mg/kg/day for 15 days) or galactosamine alone (single intraperitoneal [ip] injection on day 7 to mimic viral hepatitis) or a combination of NVP (75/ 100/150 mg/kg/day for 15 days) and galactosamine (single 750 mg/kg ip on day 7). Livers were collected at necropsy for histopathology, matrix-assisted laser desorption/ionization imaging mass spectrometry and gene expression. Eight days after galactosamine, hepatic fibrosis was noted in rats dosed with the combination of NVP and galactosamine. No fibrosis occurred with NVP alone or galactosamine alone. Gene expression data suggested a viral-like response initiated by galactosamine via RNA sensors leading to apoptosis, toll-like receptor, and dendritic cell responses. These were exacerbated by NVP-induced growth factor, retinol, apoptosis, and periostin effects. This finding supports clinical reports warning against exacerbation of fibrosis by NVP in patients with hepatitis C.

show abstract

Protective effects of lipocalin-2 (LCN2) in acute liver injury suggest a novel function in liver homeostasis

Cited by 118 publications

References 43 publications

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis

Lipocalin‐2 (NGAL/LCN2), a “help‐me” signal in organ inflammation

Drug-induced Liver Fibrosis

Contact Info

Product

Resources

About