Reply to correspondence 1 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Yoon-su Ha, Won Kim, Seung-Jin Kim Clinical and Molecular Hepatology.2025; 31(2): e226. CrossRef
Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen Clinical and Molecular Hepatology.2025; 31(2): e186. CrossRef
Background/Aims Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation.
Methods The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation.
Results MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs.
Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.
Citations
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Methylation changes of gallbladder DNA during the formation of gallstones Hongyu Xu, Jinlong Hu, Jinshan Liu, Rui Wang, Junbin Peng, Peilin Liu, Jiaming Yao, Baoqiang Cao Epigenomics.2026; 18(1): 55. CrossRef
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Reply to correspondence 2 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Nahee Hwang, Sungsoon Fang Clinical and Molecular Hepatology.2025; 31(2): e228. CrossRef
Unraveling the role of GOLM1-OPN-ABCG5 axis in MASH: Editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Yoon-su Ha, Won Kim, Seung-Jin Kim Clinical and Molecular Hepatology.2025; 31(2): 628. CrossRef
Bridging the gap: The GOLM1-OPN-ABCG5 axis in MASH and gallstone disease: Editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Nahee Hwang, Sungsoon Fang Clinical and Molecular Hepatology.2025; 31(2): 631. CrossRef
Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen Clinical and Molecular Hepatology.2025; 31(2): e186. CrossRef
GOLM1 and bile acid synthesis: Correspondence to editorial on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen Clinical and Molecular Hepatology.2025; 31(2): e189. CrossRef
Reply to correspondence 1 on “GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in MASH livers” Yoon-su Ha, Won Kim, Seung-Jin Kim Clinical and Molecular Hepatology.2025; 31(2): e226. CrossRef
Pharmacological effects and prospects of traditional Chinese medicine and its bioactive components in the prevention and treatment of urolithiasis and cholelithiasis Dan Jiang, Xiaofeng Zhou, Xiaolong Lu Letters in Drug Design & Discovery.2025; 22(12): 100274. CrossRef
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