Loss of neuraminidase 1 inhibits the activation of hepatic stellate cells through TGF-β/Smad3 signaling

Articles in Press

Document Type : Original Article

Authors

1 Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China

2 Department of Emergency, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China

10.22038/ijbms.2026.90987.19628

Abstract

Objective(s): Liver fibrosis is an abnormal wound-healing response. Neuraminidase 1 (NEU1) is a sialidase that has been reported to be involved in the development of cancers and metabolic diseases. However, the role of NEU1 in liver fibrosis remains unreported. This study explored the potential role of NEU1 in liver fibrosis.
Materials and Methods: Liver fibrosis was induced in C57BL/6J mice by using carbon tetrachloride (CCl4) and thioacetamide (TAA). The CCl4 group was established by intraperitoneal injection of CCl4 (1.0 µl/g body weight, 1:4 dilution in olive oil) twice weekly for six weeks. In the TAA group, mice were provided drinking TAA water at 300 mg/l for 12 weeks. The expression of NEU1, Collagen-1, ɑ-SMA and TIMP1 was detected by western blotting. The expression of NEU1 was measured by immunohistochemistry. Bioinformatics analysis was performed to explore the correlation between NEU1 and liver fibrosis in the GSE84044 dataset. Western blot analyses were performed to investigate the molecular mechanisms of NEU1 in hepatic stellate cells (HSCs).
Results: NEU1 expression was up-regulated in liver fibrosis tissues compared with normal liver tissues. The level of NEU1 was positively correlated with liver fibrosis in Chronic Hepatitis B (CHB) patients according to bioinformatics analysis. NEU1 levels were increased after stimulation with TGFβ in vitro. Knocking down NEU1 decreased the activation of HSCs by suppressing TGF-β/Smad3 signaling.
Conclusion: This study showed that NEU1 plays a crucial role in activating HSCs via TGF-β/Smad3 signaling. Therefore, it may be a potential therapeutic target for liver fibrosis. 

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References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 06 January 2026

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