International Session（Workshop）1(JSH・JSGE)
Thu. November 5th   9:40 - 12:00   Room 11: Portopia Hotel South Wing Topaz
IS-W1-7_H
 Nuclear matrix protein alternations associated with autophagic dysfunction in non-alcoholic fatty liver disease
Shunhei Yamashina1, Kazuyoshi Kon1, Kenichi Ikejima1
1Department of Gastroenterology, Juntendo University School of Medicine
Background: Dysfunction of autophagy is associated with the development and progression of various liver diseases. Nuclear matrix protein (NMP) has been demonstrated to participate in many cellular functions. Previously, we identified 14-3-3ζ, importin α4 and β as NMP up-regulated by loss of autophagy. We elucidated the physiological findings of NMP alternation in NAFLD.
Methods: Liver biopsy specimens were obtained from patients with NAFLD and control. Expression of 14-3-3ζ, M1 macrophage marker CD11c, oxidative stress marker 13-HODE and p62/SQSTM1 in the liver section was analyzed by immunohistochemical staining. The histological severity is assessed by NAFLD activity score (NAS). Statistical correlation among each group was evaluated by Spearman’s rank correlation coefficient analysis.
Results: Nuclear expression of 14-3-3ζ in hepatocytes was not detected in control liver, while hepatocytes with nucleus granularly expressed with 14-3-3ζ were observed in liver samples from NAFLD patients. The rate of 14-3-3ζ-positive nuclei was positively correlated with the number of hepatocytes with p62 aggregation, the number of 13-HODE-positive cells and NAS, but not the number of autophagic vesicles of hepatocytes and M1 macrophages.
Conclusion: These results suggested that hepatic steatosis causes modification of both cytoplasmic and nuclear proteins via autophagic dysfunction. Changes in NMP result in alteration of DNA topology and the interaction of various genes with the matrix. Therefore, changes in NMP due to hepatic steatosis might be contribute to cell death and carcinogenesis.
Index Term 1: autophagy
Index Term 2: nuclear matrix protein
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