MASLD development: From molecular pathogenesis toward therapeutic strategies.
10.1097/CM9.0000000000003629
- Author:
Zhu YANG
1
;
Jiahui ZHAO
1
;
Kexin XIE
1
;
Chengwei TANG
1
;
Can GAN
1
;
Jinhang GAO
2
Author Information
1. Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
2. Laboratory of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
- Publication Type:Review
- Keywords:
Hepatic stellate cells;
Hepatocytes;
Immune cells;
Kupffer cells;
Liver fibrosis;
Liver sinusoidal endothelial cells;
Metabolic dysfunction-associated steatohepatitis;
Metabolic dysfunction-associated steatotic liver disease
- MeSH:
Humans;
Fatty Liver/therapy*;
Animals;
Liver/pathology*;
Kupffer Cells/metabolism*;
Hepatocytes/metabolism*;
Hepatic Stellate Cells/metabolism*
- From:
Chinese Medical Journal
2025;138(15):1807-1824
- CountryChina
- Language:English
-
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis (MASH), liver fibrosis, cirrhosis, and relevant complications. The liver mainly comprises hepatocytes, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), immune cells (T cells, B cells), and hepatic stellate cells (HSCs). Crosstalk among these different liver cells, endogenous aberrant glycolipid metabolism, and altered gut dysbiosis are involved in the pathophysiology of MASLD. This review systematically examines advances in understanding the molecular pathogenesis of MASLD, with a focus on emerging therapeutic targets and translational clinical trials. We first delineate the crucial regulatory mechanisms involving diverse liver cells and the gut-liver axis in MASLD development. These cell-specific pathogenic insights offer valuable perspectives for advancing precision medicine approaches in MASLD treatment. Furthermore, we evaluate potential therapeutic targets and summarize clinical trials currently underway. By comprehensively updating the MASLD pathophysiology and identifying promising strategies, this review aims to facilitate the development of novel pharmacotherapies for this increasingly prevalent condition.
