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image of A Baicalin-targeted ZHX2/MMP14 Axis Attenuates Cirrhotic Portal

Abstract

Background

Given the high mortality associated with Cirrhotic Portal Hypertension (CPH) worldwide, this study investigates the mechanism by which baicalin (BA), known for its beneficial effects on cirrhosis, alleviates CPH.

Methods

The CPH model was established in Sprague-Dawley (SD) rats, followed by 4-week oral administration of 30 and 60 mg/kg/day BA. SD rats were randomly assigned to four groups (n=6/group): Con, Model, BA-30, and BA-60. Portal vein smooth muscle cells (PVSMCs, extracted from SD rats, n=6) were incubated with 5, 10 and 20 μmol/L BA. The levels of liver function indicators and von Willebrand factor (vWF) were determined by biochemical and immunohistochemical analyses, respectively. The portal pressure (PP) was examined. The liver fibrosis was detected by Sirius red staining. The levels of fibrosis-, angiogenesis- and proliferation-related indicators, zinc fingers and homeoboxes 2 (ZHX2), and matrix metallopeptidase 14 (MMP14) were quantified by Western blot. The levels of and interaction between ZHX2 and MMP14 were separately measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The proliferation and migration of PVSMCs were assessed by EdU staining and scratch test, respectively.

Results

BA up-regulated ZHX2 and down-regulated MMP14 (<0.001). BA concentration-dependently suppressed liver fibrosis, PP, and angiogenesis in the liver tissue, as well as PVSMC proliferation and migration, while enhancing liver function (<0.05). Further, according to the GRNdb database and luciferase reporter assay, ZHX2 is bound with the promoter of MMP14. ZHX2 could suppress the MMP14 level (<0.001). ZHX2 silencing reversed the effects of BA treatment on the proliferation and migration of PVSMCs, whereas MMP14 silencing could further offset the role of ZHX2 silencing in the BA-treated PVSMCs (<0.05).

Conclusion

BA up-regulates ZHX2 to reduce the level of MMP14 and alleviate CPH. Understanding the mechanisms of BA in CPH may provide a foundation for novel interventions to attenuate CPH.

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2025-04-24
2025-09-20

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A Baicalin-targeted ZHX2/MMP14 Axis Attenuates Cirrhotic Portal
Bentham Science Publishers ; https://doi.org/10.2174/0113892010349745250416105433
/content/journals/cpb/10.2174/0113892010349745250416105433
/content/journals/cpb/10.2174/0113892010349745250416105433
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  • Article Type:     Research Article
Keywords: cirrhosis ; baicalin ; Cirrhotic portal hypertension ; zinc fingers and homeoboxes 2 ; matrix metallopeptidase 14

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