Formation of p62-positive inclusion body is associated with macrophage polarization in non-alcoholic fatty liver disease - PubMed (original) (raw)
. 2018 Aug;48(9):757-767.
doi: 10.1111/hepr.13071. Epub 2018 Apr 10.
Affiliations
- PMID: 29473277
- DOI: 10.1111/hepr.13071
Formation of p62-positive inclusion body is associated with macrophage polarization in non-alcoholic fatty liver disease
Hirofumi Fukushima et al. Hepatol Res. 2018 Aug.
Abstract
Aim: Hepatic inclusion composed of autophagy-specific substrate p62 is one of the histological features of non-alcoholic fatty liver disease (NAFLD) and can be a precursor to hepatic carcinogenesis. The expression of p62 was enhanced by not only autophagic dysfunction but also oxidative stress and inflammation. M1/M2 phenotypic balance of macrophages plays a pivotal role in the progression of NAFLD. We evaluated the correlation between macrophage polarization and the formation of p62 aggregation in NAFLD.
Methods: Liver biopsy specimens from NAFLD patients were analyzed by immunohistochemical staining for M1 macrophage marker CD11c, M2 macrophage marker CD163, and p62/SQSTM1 (p62). The histological severity of NAFLD is assessed by a NAFLD activity score (NAS). The number of autophagic vesicles in hepatocytes was visualized and counted by using transmission electron microscopy.
Results: The aggregation of p62 was undetectable in control, whereas hepatocytes with p62 aggregation were observed in approximately 88% of NAFLD specimens. The number of hepatocytes with p62 aggregation was positively correlated with the number of autophagic vesicles, serum alanine aminotransferase, NAS, fibrosis, and the number of CD11c-positive cells, but not CD163-positive cells. Assembly of CD11c-positive cells was observed around hepatocytes with p62 aggregation. The ratio of CD11c/CD163-positive macrophages was significantly associated with the formation of p62 aggregation.
Conclusions: These findings indicate that chronic inflammation by M1-polarization of macrophages contributes to the disease progression from simple steatosis to non-alcoholic steatohepatitis in concert with autophagic dysfunction.
Keywords: Mallory-Denk body; NASH; autophagy.
© 2018 The Japan Society of Hepatology.
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