GPNMB as a diagnostic and predictive biomarker for metabolic dysfunction-associated steatotic liver disease and steatohepatitis
CHEN Chen
XU Hao
DU Wei
LIU Jingjing
WANG Lin
Abstract：Objective To evaluate the effectiveness of glycoprotein non-metastatic melanoma protein B(GPNMB)as a biomarker for the occurrence and progression of metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH).Methods GPNMB expression changes in whole liver and macrophages under the disease model were assessed by analyzing RNA-sequencing and single-cell RNA-sequencing data from a mouse MASH model.Meanwhile,twenty 8-week-old male C57BL/6 mice were randomly assigned to four groups:choline-deficient L-amino acid-defined(CDAA),CDAA diet group,high-fat diet(HFD)control group,and HFD group.Liver samples harvested at the experimental endpoint were assessed for GPNMB expression at mRNA and protein levels.The secretion and expression of GPNMB in the serum of MASH model mice were determined by ELISA.Following in vitro induction of macrophage polarization towards M1 and M2 phenotypes,changes in GPNMB expression were examined at the mRNA level.Results Results from animal experiments closely aligned with sequencing data analyses.GPNMB was lowly expressed in the control group,but demonstrated significant upregulation at both mRNA and protein levels in liver tissues of disease models(P＜0.01),predominantly localized to macrophages.After modeling,the secretion of GPNMB in the serum increased(P＜0.05).The expression of GPNMB was modulated by the polarization state of macrophages.Conclusion GPNMB is expected to become a biomarker for the diagnosis and treatment of MASLD and MASH.
Keywords：glycoprotein non-metastatic melanoma protein Bmetabolic dysfunction-associated steatotic liver diseasemetabolic dysfunction-associated steatohepatitislipid metabolismRNA-seqscRNA-seqmacrophage polarizationbiomarker
Publication Date：2026-06-30
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 819-826 )