Exploration of the role and mechanism of ORM1 in promoting hepatocyte proliferation
10.12206/j.issn.2097-2024.202410014
- VernacularTitle:ORM1促肝细胞增殖的作用及其机制探索
- Author:
Jinrun YANG
1
;
Xiang LI
1
;
Yang SUN
1
Author Information
1. Department of Pharmacology, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
- Publication Type:Originalarticles
- Keywords:
ORM1;
hepatocyte proliferation;
mechanism of action;
signaling pathway
- From:
Journal of Pharmaceutical Practice and Service
2025;43(5):222-227
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and signaling pathway mechanism of Orosomucoid-1（ORM1）in hepatocyte proliferation. Methods The expression data of ORM1 after liver resection from the GEO database were analyzed. The effects of ORM1 on hepatocyte proliferation were assessed after overexpressing ORM1 or supplementing exogenous ORM1 in liver cells. Cell proliferation was evaluated by the CCK8 assay. RNA sequencing （RNA-seq） was performed on liver tissues from ORM1 knockout mice and wildtype littermates to analyze gene expression, and KEGG enrichment analysis was employed to explore the molecular mechanisms by which ORM1 regulates hepatocyte proliferation. Results After partial liver resection in mice, ORM1 expression increased during the liver regeneration process. In vitro, ORM1 promoted the proliferation of murine Hepa1-6 hepatocytes and human HepG2 hepatocellular carcinoma cells. RNA-seq analysis of liver tissues from ORM1 knockout mice indicated that ORM1 influenced several proliferation-related pathways, including the PI3K-Akt, MAPK, Hippo, and Jak-Stat pathways. Upon ORM1 knockout, the expression of pro-proliferative genes such as Ctgf, Tcf7, Tead1, Il6ra, and Lepr decreased, while the expression of anti-proliferative genes such as Cish and Gadd45a increased. Conclusion ORM1 may promote hepatocyte proliferation by regulating key genes in cell proliferation-related pathways, including the PI3K-Akt, MAPK, Hippo and Jak-Stat pathways.
