Glycoprotein non-metastatic melanoma protein B expression correlates with the prognosis of acute liver injury/failure

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Keita Shimata¹  Taizo Hibi¹  Kotaro Kumagai²  Yuko Nakamura²  Sho Ijuin²  Seiichi Mawatari²  Kazuaki Tabu²  Hiromi Eguchi²  Shuji Kanmura²  Oki Taniyama²  Haruka Sakae²  Kohei Oda²  Akio Ido²  Ai Toyodome² 

[1]Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan

[2]Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

关键词: acute liver failure;    prognosis;    GPNMB;    macrophage;    M2c macrophage;   

DOI  :  10.3389/fcell.2023.1242152

 received in 2023-06-18, accepted in 2023-10-13,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Glycoprotein non-metastatic melanoma protein B (GPNMB) is expressed in macrophages during recovery from acute liver injury (ALI) in carbon tetrachloride (CCl4)-induced liver injury model mice. In this retrospective study, we assessed whether GPNMB levels in the serum and injured liver correlate with liver injury severity and prognosis in patients with ALI or acute liver failure (ALF).Methods: The study involved 56 patients with ALI or ALF who visited the Kagoshima University Hospital. Serum GPNMB level was measured over time, and the localization, proportion, origin, and phenotype of GPNMB-expressing cells in the injured liver were assessed. Finally, the phenotypes of human monocyte-derived macrophages and peripheral blood mononuclear cells (PBMCs) of patients with ALI and ALF were analyzed.Results: Peak GPNMB levels were significantly higher in patients with ALF and hepatic encephalopathy (HE), as well as in those who underwent liver transplantation or died, than in others. The peak GPNMB level correlated with prothrombin activity, prothrombin time-international normalized ratio, Model for End-stage Liver Disease score, and serum hepatocyte growth factor level. GPNMB was expressed in CD68-positive macrophages, and its level increased with the severity of liver injury. The macrophages showed the same polarization as M2c macrophages induced with interleukin-10 from human monocytes. Moreover, PBMCs from patients with ALF exhibited an immunosuppressive phenotype.Conclusion: We found that GPNMB levels in the serum and injured liver, which increased in patients with ALF, especially in those with HE, correlated with the severity of liver injury and prognosis of ALI and ALF. Moreover, GPNMB-positive macrophages exhibited the M2c phenotype. Our results indicate that persistently high GPNMB levels may be a prognostic marker in patients with ALI and ALF.

【 授权许可】

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Copyright © 2023 Kumagai, Kanmura, Mawatari, Nakamura, Eguchi, Taniyama, Toyodome, Ijuin, Sakae, Tabu, Oda, Shimata, Hibi and Ido.