Wen Zhao1, Xiaoxiao Zhang1, Mengmeng Hou1, Yuguo Zhang1, Yuhui Tang1, Lu Li1, Shiming Dong1, Lingdi Liu1, Dandan Zhao1, Wencong Li1, Yuemin Nan2. 1. Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Hebei Provincial Key Laboratory of liver fibrosis in chronic liver diseases, Shijiazhuang, China. 2. Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Hebei Provincial Key Laboratory of liver fibrosis in chronic liver diseases, Shijiazhuang, China. nanyuemin@163.com.
Abstract
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 (CCl₄)-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 CCl₄-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl₄-meidated activation of the transforming growth factor-beta (TGF-β)/Smad signaling pathway. Notably, CCl₄ 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.
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 (CCl₄)-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 CCl₄-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl₄-meidated activation of the transforming growth factor-beta (TGF-β)/Smad signaling pathway. Notably, CCl₄ 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.
Authors: Fei Liu; David Lagares; Kyoung Moo Choi; Lauren Stopfer; Aleksandar Marinković; Vladimir Vrbanac; Clemens K Probst; Samantha E Hiemer; Thomas H Sisson; Jeffrey C Horowitz; Ivan O Rosas; Laura E Fredenburgh; Carol Feghali-Bostwick; Xaralabos Varelas; Andrew M Tager; Daniel J Tschumperlin Journal: Am J Physiol Lung Cell Mol Physiol Date: 2014-12-12 Impact factor: 5.464
Authors: L Y Cui; X X Zhang; P Cui; W C Li; Y G Zhang; R Q Wang; S X Zhao; W G Ren; L L Kong; F Han; X W Yuan; L D Liu; Y Zhang; Q S Zhang; L Kong; Y M Nan Journal: Zhonghua Gan Zang Bing Za Zhi Date: 2020-05-20