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  3. FAM3B activates hepatic stellate cells to accelerate hepatic fibrosis by promoting glucose metabolism

FAM3B activates hepatic stellate cells to accelerate hepatic fibrosis by promoting glucose metabolism

  • Biochem Biophys Res Commun. 2025 Sep 23:786:152703. doi: 10.1016/j.bbrc.2025.152703.
Wu-Jun Wei 1,  Cheng Lin 2,  Shi-Hua Luo 3,  Jing-Jing Huang 4,  Ren-Tong Hu 3,  Jia-Xing Li 5,  Hai-Zhi Ma 6,  Jia-Zhu Wei 3,  Chun-Fang Wang 3,  Crystale-Siew-Ying Lim 7,  Yi-Bin Deng 8
Affiliations

Affiliations

  • 1 Department of Biotechnology, Faculty of Applied Sciences, UCSI Heights, UCSI University, No 1 Jalan UCSI, Cheras, Taman Connaught, 56000, Kuala Lumpur, Malaysia; Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China; Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Baise, Guangxi, 533000, China; Key Laboratory of Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases of Baise, Baise, Guangxi, 533000, China.
  • 2 Department of Interventional Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China.
  • 3 Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China.
  • 4 Department of Health Care, Baise Maternal and Child Health Hospital, Baise, Guangxi, 533000, China.
  • 5 Department of Pharmacy, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China.
  • 6 Department of Ultrasound Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China.
  • 7 Department of Biotechnology, Faculty of Applied Sciences, UCSI Heights, UCSI University, No 1 Jalan UCSI, Cheras, Taman Connaught, 56000, Kuala Lumpur, Malaysia. Electronic address: crystalelim@ucsiuniversity.edu.my.
  • 8 Center for Clinical Laboratory Diagnosis and Research, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China; Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Baise, Guangxi, 533000, China; Key Laboratory of Research and Development on Clinical Molecular Diagnosis for High-Incidence Diseases of Baise, Baise, Guangxi, 533000, China. Electronic address: dengyb75@163.com.
PMID: 41027184 DOI: 10.1016/j.bbrc.2025.152703
Abstract

This study aimed to investigate the role and mechanism of FAM3B (family with sequence similarity 3 member B) in hepatic fibrosis. Bioinformatics analysis, immunohistochemistry, Masson staining, and immunofluorescence detection revealed that the expression of FAM3B was significantly elevated in human hepatic fibrosis tissues and positively correlated with serum HBV DNA load and Collagen deposition. Using lentiviral overexpression of FAM3B in the HSC-T6 cell model and siRNA knockdown experiments, we confirmed that FAM3B overexpression promotes hepatic stellate cell (HSC) activation by enhancing glucose metabolism (indicated by increased glucose uptake, upregulation of key glycolytic Enzymes GLUT1, GLUT3, HK2, LDHA, PFKP, and PKM2, elevated extracellular acidification rate, and increased lactate production) and upregulating HK2 promoter transcriptional activity. This leads to increased α-SMA and COL1α1 expression, enhanced cell proliferation, and suppressed Apoptosis, effects that were reversed by the glycolysis inhibitor 2-deoxyglucose (2-DG). In vivo, FAM3B overexpression exacerbated CCl4-induced liver fibrosis and Collagen deposition in mice, while 2-DG intervention significantly alleviated this process. CONCLUSION: FAM3B accelerates HSC activation and hepatic fibrosis progression by enhancing glucose metabolism.

Keywords

FAM3B; Glucose metabolism; Hepatic fibrosis; Hepatic stellate cells activation.

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