Hepatic Mac2‐BP expression depends on liver fibrosis and inflammation due to fat accumulation in patients with metabolic dysfunction‐associated steatotic liver disease

Author:

Uojima Haruki12,Tsujikawa Hanako34,Yamazaki Ken45,Sugiyama Masaya6ORCID,Take Akira7,Sakaguchi Yoshihiko8,Gotoh Kazuyoshi9,Satoh Takashi10,Hidaka Hisashi2ORCID,Hayashi Shunji6,Kusano Chika2,Sakamoto Michiie411,Mizokami Masashi1

Affiliation:

1. Genome Medical Sciences Project Research Institute National Center for Global Health and Medicine Ichikawa Chiba Japan

2. Department of Gastroenterology Internal Medicine Kitasato University School of Medicine Sagamihara Kanagawa Japan

3. Department of Diagnostic Pathology National Hospital Organization Saitama Hospital Wako Japan

4. Department of Pathology Keio University School of Medicine Shinjuku Tokyo Japan

5. Division of Molecular Pathology Research Institute Tochigi Cancer Center Utsunomiya Tochigi Japan

6. Department of Viral Pathogenesis and Controls Research Institute National Center for Global Health and Medicine Ichikawa Chiba Japan

7. Department of Microbiology Kitasato University School of Medicine Sagamihara Kanagawa Japan

8. Department of Microbiology Faculty of Pharmaceutical Sciences Tokushima Bunri University Yamashiro‐cho Tokushima Japan

9. Department of Bacteriology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan

10. Division of Hematology Kitasato University School of Allied Health Sciences Sagamihara Kanagawa Japan

11. Department of Pathology School of Medicine International University of Health and Welfare Narita Chiba Japan

Abstract

AbstractAimData on the upregulation of Mac‐2 binding protein (M2BP) expression associated with fat accumulation in the liver are limited. Therefore, we aimed to assess the relationship between hepatic M2BP expression and changes in the liver microenvironment due to fat accumulation in patients with metabolic dysfunction associated steatotic liver disease (MASLD).MethodsLiver specimens obtained from 46 patients with MASLD were subjected to immunohistochemical staining to visualize M2BP expression in the liver. The staining intensity in the hepatocytes and sinusoidal cells was classified as high or low grade. First, the correlation between hepatic M2BP expression and microenvironmental changes caused by fat accumulation was examined. Then, the influence of hepatic M2BP expression on serum M2BP glycosylation isomer levels in patients with MASLD was evaluated.ResultsThe staining grade of M2BP was higher in the sinusoidal cells than in the hepatocytes (p = 0.015). The patients with high staining grade in their hepatocytes had more severe lobular inflammation than those with low staining grade (p = 0.037). Additionally, the patients with high staining grade in their sinusoidal cells presented more severe fibrosis than those with low staining grade (p = 0.018). The staining grade in the hepatocytes correlated positively with serum M2BP glycosylation isomer levels (p = 0.023), whereas no correlation was observed between sinusoidal staining grade and serum M2BP glycosylation isomer levels (p = 0.393).ConclusionsFat accumulation in patients with MASLD leads to M2BP expression in hepatocytes due to liver inflammation and that in sinusoidal cells due to fibrosis.

Publisher

Wiley

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