Universität zu Köln

Churin, Yuri, Irungbam, Karuna, Imiela, Christoph S., Schwarz, David, Mollenkopf, Hans-Joachim, Drebber, Uta, Odenthal, Margarete, Pak, Oleg, Huber, Magdalena ORCID: 0000-0002-2963-0693, Glebe, Dieter, Roderfeld, Martin and Roeb, Elke (2021). Lipid Storage and Interferon Response Determine the Phenotype of Ground Glass Hepatocytes in Mice and Humans. Cell. Mol. Gastroenterol. Hepatol., 12 (2). S. 383 - 395. SAN DIEGO: ELSEVIER INC. ISSN 2352-345X

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Abstract

BACKGROUND AND AIMS: A histopathological hallmark of chronic hepatitis B virus (HBV) infection is the presence of ground glass hepatocytes (GGHs). GGHs are liver cells that exhibit eosinophilic, granular, glassy cytoplasm in light microscopy and are characterized by accumulation of HBV surface (HBs) proteins in the endoplasmic reticulum (ER). More important, GGHs have been accepted as a precursor of HCC and may represent preneoplastic lesions of the liver. METHODS: Here we show that the reason for ground glass phenotype of hepatocytes in patients with chronic hepatitis B (CHB) and in HBs transgenic mice is a complex formation between HBs proteins and lipid droplets (LDs) within the ER. RESULTS: As fat is a main component of LDs their presence reduces the protein density of HBs aggregates. Therefore, they adsorb less amount of eosin during hematoxylin-eosin staining and appear dull in light microscopy. However, after induction of interferon response in the liver LDs were not only co-localized with HBs but also distributed throughout the cytoplasm of hepatocytes. The uniform distribution of LDs weakens the contrast between HBs aggregates and the rest of the cytoplasm and complicates the identification of GGHs. Suppression of interferon response restored the ground glass phenotype of hepatocytes. CONCLUSIONS: Complex formation between HBs and LDs represents a very important feature of CHB that could affect LDs functions in hepatocytes. The strain specific activation of the interferon response in the liver of HBs/c mice prevented the development of GGHs. Thus, manipulation of LDs could provide a new treatment strategy in the prevention of liver cancer.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Churin, Yuri UNSPECIFIED UNSPECIFIED UNSPECIFIED Irungbam, Karuna UNSPECIFIED UNSPECIFIED UNSPECIFIED Imiela, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Mollenkopf, Hans-Joachim UNSPECIFIED UNSPECIFIED UNSPECIFIED Drebber, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Pak, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Huber, Magdalena UNSPECIFIED orcid.org/0000-0002-2963-0693 UNSPECIFIED Glebe, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Roderfeld, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Roeb, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-594168
DOI:	10.1016/j.jcmgh.2021.03.009
Journal or Publication Title:	Cell. Mol. Gastroenterol. Hepatol.
Volume:	12
Number:	2
Page Range:	S. 383 - 395
Date:	2021
Publisher:	ELSEVIER INC
Place of Publication:	SAN DIEGO
ISSN:	2352-345X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEPATITIS-B-VIRUS; PRE-S MUTANTS; LARGE ENVELOPE POLYPEPTIDE; SURFACE-ANTIGEN; FAMILY; LIVER; PROTEINS; REPLICATION; ACTIVATION; EXPRESSION Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59416