Characterization of two types of intranuclear hepatocellular inclusions in NAFLD.
Adult
Aged
Autophagy
/ genetics
Cathepsin B
/ metabolism
Cathepsin D
/ metabolism
Disease Progression
Female
Hepatocytes
/ cytology
Humans
Intranuclear Inclusion Bodies
/ metabolism
Male
Microtubule-Associated Proteins
/ metabolism
Middle Aged
Non-alcoholic Fatty Liver Disease
/ genetics
Sequestosome-1 Protein
/ metabolism
Ubiquitin
/ metabolism
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 10 2020
06 10 2020
Historique:
received:
22
02
2020
accepted:
26
06
2020
entrez:
7
10
2020
pubmed:
8
10
2020
medline:
5
2
2021
Statut:
epublish
Résumé
Nuclear inclusions (NI) are a common finding in hepatocytes from patients with liver disease especially in diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) but studies examining the shape and content of these inclusions in detail are lacking. In this study we define two distinct types of NI in NAFLD: inclusions bounded by the nuclear membrane, containing degenerative cell organelles and heterolysosomes (type1) and inclusions with deposits of glycogen but without any kind of organelles and delimiting membrane (type2). NI in 77 paraffin-embedded patients of NAFLD including NAFL and non-alcoholic steatohepatitis (NASH) were analyzed. In 4-12% of type1 NI immunopositivity for the autophagy-associated proteins LC3B, ubiquitin, p62/sequestosome1, cathepsin D and cathepsin B were detected with co-localizations of ubiquitin and p62; type2 NI showed no immunoreactivity. Three-dimensional reconstructions of isolated nuclei revealed that NI type1 are completely enclosed within the nucleus, suggesting that NI, although probably derived from cytoplasmic invaginations, are not just simple invaginations. Our study demonstrates two morphologically different types of inclusions in NAFLD, whereby both gained significantly in number in advanced stages. We suggest that the presence of autophagy-associated proteins and degenerated organelles within type1 NI plays a role in disease progression.
Identifiants
pubmed: 33024131
doi: 10.1038/s41598-020-71646-y
pii: 10.1038/s41598-020-71646-y
pmc: PMC7538976
doi:
Substances chimiques
MAP1LC3B protein, human
0
Microtubule-Associated Proteins
0
SQSTM1 protein, human
0
Sequestosome-1 Protein
0
Ubiquitin
0
CTSB protein, human
EC 3.4.22.1
Cathepsin B
EC 3.4.22.1
CTSD protein, human
EC 3.4.23.5
Cathepsin D
EC 3.4.23.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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