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

Kotaro Kumagai; Shuji Kanmura; Seiichi Mawatari; Yuko Nakamura; Hiromi Eguchi; Oki Taniyama; Ai Toyodome; Sho Ijuin; Haruka Sakae; Kazuaki Tabu; Kohei Oda; Keita Shimata; Taizo Hibi; Akio Ido

doi:10.3389/fcell.2023.1242152

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

Front Cell Dev Biol. 2023 Oct 24:11:1242152. doi: 10.3389/fcell.2023.1242152. eCollection 2023.

Authors

Affiliations

¹ Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
² Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.

Abstract

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.

Keywords: GPNMB; M2c macrophage; acute liver failure; macrophage; prognosis.

Grants and funding

This work was supported by the Japanese Ministry of Health, Labour and Welfare Research Program on Intractable Hepatobiliary Disease, Grant Number JPMH20FC1023.