Potential Role of Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a Mediator of Liver Injury and Fibrogenesis in Alcoholic Hepatitis

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  • May 4, 2020
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  • Patel, Palak K.
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
Abstract
  • Background: Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease (ALD) associated with significant short-term mortality. Existing treatment therapies are not completely effective, highlighting the need to identify molecular drivers in AH. NGAL has recently been identified as one of the most overexpressed genes in patients with AH. Aims: To investigate the role of NGAL as a potential target for therapy in AH using a translational approach including human samples and animal models. Methods: NGAL expression was analyzed in patients with AH, animal models of liver inflammation and fibrogenesis, and cell lines of human hepatocytes. Fibrosis- and inflammation-marker genes were analyzed for expression in hepatic stellate cell (HSC) cell lines treated with NGAL. RNA was extracted from all samples and gene expression of cDNA was measured using real-time qPCR analysis. Results: Gene expression of NGAL in patients with AH had a 44-fold increase in comparison to several other liver diseases. Animal models of liver inflammation and fibrosis had increased NGAL expression. Although cell lines of human hepatocytes exhibited greater NGAL expression than HSC cell lines, there was no noticeable increase in NGAL expression with subsequent pro-inflammatory induction of hepatocyte cell lines. HSC cell lines showed increased expression of several markers of fibrosis and inflammation with NGAL treatment. Conclusion: NGAL is overexpressed in patients with AH and in animal models of liver inflammation and fibrosis and it exerts fibrogenic and inflammatory effects in hepatic stellate cells. Results suggest that NGAL may be a potential target for therapy in AH. Further studies should be done to more fully explore the nature of NGAL overexpression in AH.
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  • In Copyright
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  • Funding: None
Advisor
  • Bataller, Ramon
Degree
  • Bachelor of Science in Public Health
Honors level
  • Highest Honors
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2014
Language
  • English
Extent
  • 19

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