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Unraveling key molecules mediating the mechanisms of YAP deletion or inhibition in liver fibrosis regression through a multi-omics approach

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Wang-41-831-848-2026.pdf(15.32 MB)
Date
2026
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Authors
Shihui Liu ; Hejing Ruan ; Yuzhe Cheng ; Yan Qiao ; Jiawei Wang ; Xiaojun Liu ; Chuanmiao Liu ; Wen Zhao ; Siyuan Wang
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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BiologĂ­a Celular e HistologĂ­a
DOI
https://doi.org/10.14670/HH-18-993
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info:eu-repo/semantics/article
Description
Abstract
Background. This study aimed to identify key molecules that potentially mediate the mechanisms by which YAP deletion or inhibition attenuates liver fibrosis. Materials and Methods. C57BL/6 mice were divided into four groups: control, carbon tetrachloride (CCl4), CCl4-YAP-HKO, and CCl4-verteporfin (VP). RNA sequencing (RNA-seq) and proteomic analysis were conducted. Immunohistochemistry and western blotting were also performed to verify the differentially expressed genes (DEGs) identified through the multi omics approach. Human subjects were enrolled to further assess the identified DEGs. Results. In comparison with the CCl4 group, both the CCl4-YAP-HKO and CCl4-VP groups exhibited liver fibrosis regression. RNA-seq and proteomic analyses identified 12 commonly differentially expressed molecules. Immunohistochemistry and western blotting validated that heat shock protein 27 (HSP27), heat shock protein 70 (HSP70), and p62 expression were significantly reduced, and milk fat globule-epidermal growth factor 8 (MFGE8) expression was elevated in both the CCl4-YAP-HKO and CCl4-VP groups compared with the CCl4 group. Furthermore, plasma p62, HSP27, and HSP70 levels were increased with the occurrence of chronic hepatitis B and HBV-related cirrhosis, whereas MFGE8 levels were decreased. Spearman’s correlation analysis further illustrated a significant association between these biomarkers and YAP levels. Conclusions. This study identified HSP27, HSP70, p62, and MFGE8 as crucial YAP-related molecules involved in liver fibrosis.
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Yes-associated protein , RNA sequencing , roteome sequencing , Verteporfin , Liver fibrosis
Citation
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http://hdl.handle.net/10201/230321
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Histology and histopathology, Vol.41, NÂş5, (2026)
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