Scientific reports, 2020-10, Vol.10 (1), p.16533-16533, Article 16533
2020
Details
- Autor(en) / Beteiligte
- Titel
- Characterization of two types of intranuclear hepatocellular inclusions in NAFLD
- Ist Teil von
- Scientific reports, 2020-10, Vol.10 (1), p.16533-16533, Article 16533
- Ort / Verlag
- England: Nature Publishing Group UK
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-020-71646-yTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7538976
- Format
- –
- Schlagworte
- Adult, Aged, Autophagy - genetics, Cathepsin B - metabolism, Cathepsin D - metabolism, Disease Progression, Female, Hepatocytes - cytology, Humans, Intranuclear Inclusion Bodies - metabolism, Intranuclear Inclusion Bodies - pathology, Male, Microtubule-Associated Proteins - metabolism, Middle Aged, Non-alcoholic Fatty Liver Disease - genetics, Non-alcoholic Fatty Liver Disease - metabolism, Non-alcoholic Fatty Liver Disease - pathology, Sequestosome-1 Protein - metabolism, Ubiquitin - metabolism, Young Adult