Portal hypertension contributes to ascites formation via the Piezo1−nuclear factor kappa-B−aquaporin1 pathway in liver cirrhosis
Open accessAbstract
Portal hypertension is critical to the development of ascites in liver cirrhosis. The aim of our study was to evaluate the contribution of portal hypertension to ascites formation and explore the underlying mechanism. Here, the role of portal hypertension in cirrhotic ascites was determined through a meta-analysis of portal pressure in cirrhotic patients and animal models. The mechanism underlying the involvement of portal hypertension in ascites formation was explored. The meta-analysis showed hepatic venous pressure gradient in patients with cirrhosis with ascites was significantly higher than that in patients with cirrhosis without ascites. In carbon tetrachloride (CCl 4 )-treated rats, portal pressure of cirrhotic rats with ascites (19.83 cmH 2 O) was significantly higher than that in cirrhotic rats without ascites (14.90 cmH 2 O). In a novel murine model created by thioacetamide (TAA)/CCl 4 administration plus partial portal vein ligation (PPVL), a significant increase in portal pressure and ascites amount was observed in the TAA/CCl 4 + PPVL group compared with the TAA/CCl 4 group. In the mice treated with TAA/CCl 4 plus PPVL, the amount of ascites decreased significantly in mice with endothelial deletion of Piezo1 (Piezo1 △EC ) compared with Piezo1 flox/flox mice. Finally, Piezo1 in liver sinusoidal endothelial cells and peritoneal endothelial cells promoted the development of portal hypertensive ascites via the nuclear factor kappa-B (NF-ĸB)−aquaporin1 (AQP1) pathway. In conclusion, Piezo1 in endothelium contributes to the formation of portal hypertensive ascites via the NF-ĸB−AQP1 pathway in liver cirrhosis, which indicates that blockage of the Piezo1−NFĸB−AQP1 pathway may be a useful strategy for the management of ascites in liver cirrhosis.
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GsMTx4 is not entirely specific for Piezo1.
“Because GsMTx4 is not entirely specific for Piezo1 [42, 43]”
From Liver Stiffness Rises Early in MASLD and Drives Inflammation, Lipid Dysmetabolism, and Fibrosis via Piezo1–YAP Mechanotransduction (2026) · cites this paper as [43]
The Introduction and Results discuss Piezo1 and experiments using endothelial cell-specific Piezo1 deletion, but do not address whether GsMTx4 is specific for Piezo1. Searches for “GsMTx4” and for inhibitor specificity found no passage on that point in our copy. (LLM, conf=0.73)
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Self-citation
- Authors
- Wei, N., Du, L., Xiao, Z., Zhang, L., Zhou, Y., Gao, H., Liu, M., Wang, C., Hou, X., Li, Y., & Song, Y.
- Affiliations
- Wuhan Union Hospital (CN)
- Kunming University of Science and Technology (CN)
- Corresponding author
- Li, Yan
- Song, Yuhu
- Venue
- Experimental & Molecular Medicine
- Published
- 2025-10-01
- Volume
- 57
- Issue
- 10
- Pages
- 2305-2316
- ISSN
- 1226-3613 (ISSN-L)
- 2092-6413
- PMC
- PMC12586457
- OpenAlex
- W4414707102
- Cited by
- 3
- References
- 54
- Citations by year
- 2026: 1 · 2025: 2
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Experimental & Molecular Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82470662, 82070631)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- portal hypertension, cirrhotic ascites, Piezo1, NF-κB, aquaporin-1, liver cirrhosis, liver sinusoidal endothelial cells, hepatic venous pressure gradient, partial portal vein ligation, thioacetamide, carbon tetrachloride, endothelial mechanosensing
- MeSH terms
- Systematic Reviews as Topic, Animals, Ascites, Carbon Tetrachloride, Disease Models, Animal, Humans, Hypertension, Portal, Ion Channels, Liver Cirrhosis, Male, Thioacetamide, Meta-Analysis as Topic, Signal Transduction, NF-kappa B, Mice, Rats, Aquaporin 1
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