Browsing by Subject "Yes-associated protein"

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    Differential expression of Yes-associated protein and phosphorylated Yes-associated protein is correlated with expression of Ki-67 and phospho-ERK in colorectal adenocarcinoma
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Kim, Dong-Hoon; Kim, Seok-Hyung; Lee, Ok-Jun; Huang, Song-Mei; Kwon, Ju-Lee; Kim, Jin Man; Kim, Ji-Yeon; Seong, In Ock; Song, Kyu Sang; Kim, Kyung Hee
    Yes-associated protein (YAP) is a transcriptional co-activator and functions as a nuclear downstream effector of the Hippo pathway. Differential expression of YAP and phosphorylated Yes-associated protein (pYAP), which are involved in the expression of Ki-67 and phosphorylated extracellular signal-regulated kinase (pERK) in colorectal adenocarcinoma (CRAC), is not clear. Herein, we hypothesized that nuclear expression of YAP could predict cell proliferation and poor prognosis, while cytoplasmic expression of pYAP would show a reverse correlation with cell proliferation. Paraffin-embedded samples from 144 CRAC patients were studied using immunohistochemistry for YAP, pYAP, Ki-67 and pERK. Frozen samples from 20 CRAC patients were examined for YAP mRNA in tumor and non-tumor tissues, using quantitative real-time PCR. High nuclear YAP expression coincided with high Ki-67 expression (P=0.002). The high nuclear YAP expression group tended to display a poor overall and disease-free survival (P=0.089 and P=0.089, respectively), but YAP mRNA levels in the 20 CRAC tissues were not significantly different in comparison with the 20 nontumor tissues (P=0.929). We observed an inverse correlation between high cytoplasmic pYAP expression and high Ki-67 expression (P=0.001). Nuclear pERK expression was positively correlated with nuclear YAP expression, but negatively correlated with cytoplasmic pYAP expression (P=0.017 and P=0.020, respectively). Activated nuclear YAP and inactivated cytoplasmic pYAP in CRAC showed a positive correlation with Ki67 and nuclear pERK expression, suggesting that the expression of YAP and pYAP is a possible predictor of tumor cell proliferation and prognosis in CRAC.
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    Traditional Chinese medicine Yiqi Huoxue recipe attenuates hepatic fibrosis via YAP/TAZ signaling
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Zhao, Wen; Zhang, Xiaoxiao; Hou, Mengmeng; Zhang, Yuguo; Tang, Yuhui; Li, Lu; Dong, Shiming; Liu, Lingdi; Zhao, Dandan; Li, Wencong; Nan, Yuemin
    Background/Aims. The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis. Materials and Methods. Wistar rats were used to generate a model of carbon tetrachloride (CCl 4)-induced liver fibrosis. Chronic hepatitis B (CHB) patients with liver fibrosis were enrolled and assigned to receive either nucleoside/nucleotide analogues (NAs) or NAs plus YQHX. Histology, immunohistochemistry, qRT-PCR, and western blotting were conducted to mechanistically assess the therapeutic effects of YQHX on liver fibrosis. Results. YQHX markedly alleviated morphological alterations in CCl 4-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl 4-meidated activation of the transforming growth factor-beta (TGF-β)/Smad signaling pathway. Notably, CCl 4 induced up-regulation of YAP, TAZ, and connective tissue growth factor (CTGF), which were significantly abrogated by YQHX. Consistent with the above major findings in rats, CHB patients treated with NAs plus YQHX had greater improvement in liver fibrosis than those given NAs alone (71.4% vs. 28.6%; P=0.057). In addition, hepatic and plasma levels of YAP were significantly decreased after YQHX treatment in CHB patients with liver fibrosis. Conclusion. YAP/TAZ signaling plays a role, at least in part, in the anti-fibrotic activity of YQHX. The findings may help to better understand the mechanisms of YQHX in the treatment of liver fibrosis
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    Unraveling key molecules mediating the mechanisms of YAP deletion or inhibition in liver fibrosis regression through a multi-omics approach
    (2026) Shihui Liu; Hejing Ruan; Yuzhe Cheng; Yan Qiao; Jiawei Wang; Xiaojun Liu; Chuanmiao Liu; Wen Zhao; Siyuan Wang; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    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.