Article
Biochemistry & Molecular Biology
Sixian Qi, Zhenxing Zhong, Yuwen Zhu, Yebin Wang, Mingyue Ma, Yu Wang, Xincheng Liu, Ruxin Jin, Zhihan Jiao, Rui Zhu, Zhao Sha, Kyvan Dang, Ying Liu, Dae-Sik Lim, Junhao Mao, Lei Zhang, Fa-Xing Yu
Summary: This study reveals that the HPO1 and HPO2 modules together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators in the Hippo pathway. Inactivation of either HPO1 or HPO2 module leads to partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC) in mice livers. On the other hand, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality.
Article
Biochemistry & Molecular Biology
Rui Wang, Yi Ren, Ting Bao, Ting Wang, Yiwei Li, Yuanyuan Liu, Xiaoxia Zhang, Shaoqi Yang, Hao Wang
Summary: Inulin reverses lipid metabolism disorders and abnormal accumulation of bile acids in NAFLD mice by modulating bile acids signaling.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Claudia D. Fuchs, Natalie Sroda, Hubert Scharnagl, Ruchi Gupta, Wesley Minto, Tatjana Stojakovic, John T. Liles, Grant Budas, David Hollenback, Michael Trauner
Summary: This study demonstrates that cilofexor, a non-steroidal FXR agonist, improves cholestatic liver injury and hepatic fibrosis in the Mdr2-/-mouse model of sclerosing cholangitis. These findings suggest the potential therapeutic properties of cilofexor in cholestatic liver diseases, mediated by intestinal FXR-mediated gut-liver signaling.
Review
Biochemistry & Molecular Biology
Takeshi Katafuchi, Makoto Makishima
Summary: Bile acids have detergent and hormone-like properties. FXR and FGF15/19 are considered as potential therapeutic targets for metabolic syndrome and cholestatic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Juan Li, Hanxiang Zhan, Yidan Ren, Maoxiao Feng, Qin Wang, Qinlian Jiao, Yuli Wang, Xiaoyan Liu, Shujun Zhang, Lutao Du, Yunshan Wang, Chuanxin Wang
Summary: This study found that SIRT4 activates the phosphorylation of p53 protein and promotes autophagy in PDAC by suppressing glutamine metabolism, thereby inhibiting tumor growth and progression.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Medicine, Research & Experimental
Tao Chen, Zhiqing Yuan, Zhou Lei, Jinlin Duan, Junyan Xue, Ting Lu, Guouan Yan, Lei Zhang, Yanfeng Liu, Qiwei Li, Yonglong Zhang
Summary: This study uncovers a metabolic vulnerability and mTOR addiction in HCC with HPCAL1 loss, providing a selective therapeutic window for HCC with mTORC1 hyperactivation using mTORi.
Review
Biochemistry & Molecular Biology
Jing Zeng, Jiangao Fan, Huiping Zhou
Summary: Chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), gradually progress to liver fibrosis, cirrhosis, and failure. Disruption of bile acid metabolism and intrahepatic circulation plays a crucial role in accelerating the progression of cholestatic liver diseases. Bile acids not only act as detergents for nutrition absorption but also function as key signaling molecules that regulate hepatic metabolism and immune responses. This review focuses on the role of bile acid-mediated signaling in cholestatic liver disease.
CELL AND BIOSCIENCE
(2023)
Article
Cell Biology
Yixuan Qiu, Jiaming Yu, Xueying Ji, Huiyuan Yu, Mengjuan Xue, Fan Zhang, Yi Li, Zhijun Bao
Summary: This study found that ileal FXR-FGF15/19 signaling was downregulated in older men and aged male mice due to changes in gut microbiota and microbial bile acid metabolism during aging. Ileal FXR activation increased skeletal muscle mass and improved muscle performance in aged mice, suggesting that ileal FXR-FGF15/19 signaling is a potential therapeutic target for sarcopenia.
MECHANISMS OF AGEING AND DEVELOPMENT
(2022)
Article
Oncology
Yabing Nan, Qingyu Luo, Xiaowei Wu, Shi Liu, Pengfei Zhao, Wan Chang, Aiping Zhou, Zhihua Liu
Summary: This study identifies D-AS2 as a targetable lipid-related long noncoding RNA that increases phospholipase D activity to promote YAP signaling, triggering chemoresistance in SCC.
Article
Pharmacology & Pharmacy
Yifei Lu, Mingmei Shao, Caiyun Zhang, Hongjiao Xiang, Junmin Wang, Tao Wu, Guang Ji
Summary: This study investigated the effects of kaempferol on non-alcoholic steatohepatitis (NASH) in mice by analyzing bile acids (BAs) and gene expression. The results showed that kaempferol can increase certain BAs levels, decrease others, and regulate the expression of genes related to BA metabolism, thus improving NASH.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Endocrinology & Metabolism
Linda X. Wang, Mark R. Frey, Rohit Kohli
Summary: Bile acids not only play a crucial role in lipid digestion, but also act as signaling molecules in metabolic processes throughout the body. By binding to various receptors, bile acids regulate glucose and lipid metabolism, and promote glycogen synthesis. Recent studies have identified a novel intestinal protein that positively affects bile acid levels, providing a new target for treating metabolic and bile acid-related disorders.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Yoichi Takimoto, Po-sung Chu, Nobuhiro Nakamoto, Yuya Hagihara, Yohei Mikami, Kentar Miyamoto, Rei Morikawa, Toshiaki Teratani, Nobuhito Taniki, Sota Fujimori, Takahiro Suzuki, Yuzo Koda, Rino Ishihara, Masataka Ichikawa, Akira Honda, Takanori Kanai
Summary: The resolution process of liver fibrosis after liver injury withdrawal is still not fully understood. In this study, the pro-fibrogenic role of Toll-like receptor 4 (TLR4) signaling in tissue fibroblasts was explored. Interestingly, pharmacological inhibition of TLR4 signaling in vivo in two murine models resulted in a significant delay in fibrosis resolution. Single-cell transcriptome analysis revealed a cluster of Tlr4-expressing myeloid cells that played a restorative role in the resolution process. Further investigation suggested a microbiome-dependent nature of the delayed resolution after gut sterilization. These findings provide insights into the pro-fibrolytic role of myeloid TLR4 signaling and potential targets for anti-fibrotic therapy.
Review
Biology
Wei Jia, Yitao Li, Kenneth C. P. Cheung, Xiaojiao Zheng
Summary: Bile acids play a crucial role in nutrient absorption and act as key regulators of lipid and glucose metabolism and immune homeostasis. They interact with receptors in all major organs, leading to organ-organ interactions that regulate both local and global metabolic processes, as well as the immune system. Targeting BA synthesis and receptor signaling is a promising strategy for the development of novel therapies for various diseases throughout the body.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Juan F. Burgueno, Julia Fritsch, Eddy E. Gonzalez, Kevin S. Landau, Ana M. Santander, Irina Fernandez, Hajar Hazime, Julie M. Davies, Rebeca Santaolalla, Matthew C. Phillips, Sophia Diaz, Rishu Dheer, Nivis Brito, Judith Pignac-Kobinger, Ester Fernandez, Gregory E. Conner, Maria T. Abreu
Summary: Chronic colonic inflammation can lead to dysplasia and cancer. Activation of TLR4 is associated with up-regulation of DUOX2 and NOX1, leading to increased epithelial production of H2O2, promoting colorectal tumor formation.
Article
Gastroenterology & Hepatology
Youn-Sang Jung, Sabrina A. Stratton, Sung Ho Lee, Moon-Jong Kim, Sohee Jun, Jie Zhang, Biyun Zheng, Christopher L. Cervantes, Jong-Ho Cha, Michelle C. Barton, Jae-Il Park
Summary: The study reveals that TMEM9 hyperactivates Wnt signaling for liver regeneration and tumorigenesis through lysosomal degradation of APC. TMEM9 is highly expressed in regenerating liver and hepatocellular carcinoma (HCC) cells. In HCC, TMEM9 is overexpressed and necessary to maintain beta-catenin hyperactivation.
Article
Chemistry, Multidisciplinary
Mei Chen, Zhide Guo, Qinghua Chen, Jingping Wei, Jingchao Li, Changrong Shi, Duo Xu, Dawang Zhou, Xianzhong Zhang, Nanfeng Zheng
Article
Cell Biology
Bo Zhou, Jia-yuan Zhang, Xian-shuo Liu, Hang-zi Chen, Yuan-li Ai, Kang Cheng, Ru-yue Sun, Dawang Zhou, Jiahuai Han, Qiao Wu
Article
Multidisciplinary Sciences
Ping Wang, Jing Geng, Jiahui Gao, Hao Zhao, Junhong Li, Yiran Shi, Bingying Yang, Chen Xiao, Yueyue Linghu, Xiufeng Sun, Xin Chen, Lixin Hong, Funiu Qin, Xun Li, Jau-Song Yu, Han You, Zengqiang Yuan, Dawang Zhou, Randy L. Johnson, Lanfen Chen
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Qiyao Chai, Xudong Wang, Lihua Qiang, Yong Zhang, Pupu Ge, Zhe Lu, Yanzhao Zhong, Bingxi Li, Jing Wang, Lingqiang Zhang, Dawang Zhou, Wei Li, Wenzhu Dong, Yu Pang, George Fu Gao, Cui Hua Liu
NATURE COMMUNICATIONS
(2019)
Review
Cell Biology
Shihao Zhang, Dawang Zhou
CURRENT OPINION IN CELL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Jing Geng, Yiran Shi, Jinjia Zhang, Bingying Yang, Ping Wang, Weihong Yuan, Hao Zhao, Junhong Li, Funiu Qin, Lixin Hong, Changchuan Xie, Xianming Deng, Yujie Sun, Congying Wu, Lanfen Chen, Dawang Zhou
Summary: TLR4 signaling enhances macrophage bactericidal activity through the mechanical sensor Piezo1, with mechanical sensing signals playing a critical role in the innate immune response. The assembly of Piezo1 and TLR4 complex triggers the remodeling of F-actin organization to augment phagocytosis and bacterial clearance, providing insights into macrophage mechanophysiology and host response coordination.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Qingxu Liu, Jiaxin Li, Weiji Zhang, Chen Xiao, Shihao Zhang, Cheng Nian, Junhong Li, Dongxue Su, Lihong Chen, Qian Zhao, Hui Shao, Hao Zhao, Qinghua Chen, Yuxi Li, Jing Geng, Lixin Hong, Shuhai Lin, Qiao Wu, Xianming Deng, Rongqin Ke, Jin Ding, Randy L. Johnson, Xiaolong Liu, Lanfen Chen, Dawang Zhou
Summary: Glucose consumption is increased in tumor cells to support tumor growth, while glycogen accumulation plays a crucial role in liver malignant transformation. Glycogen accumulation blocks Hippo signaling and enhances tumor incidence in cancer-initiating cells.
Article
Biochemistry & Molecular Biology
Sixian Qi, Yuwen Zhu, Xincheng Liu, Pengyue Li, Yebin Wang, Yan Zeng, Aijuan Yu, Yu Wang, Zhao Sha, Zhenxing Zhong, Rui Zhu, Haixin Yuan, Dan Ye, Shenglin Huang, Chen Ling, Yanhui Xu, Dawang Zhou, Lei Zhang, Fa-Xing Yu
Summary: The study reveals that WWC proteins interact directly with LATS1/2 and SAV1, and SAV1 brings in MST1/2 to phosphorylate and activate LATS1/2. Additionally, a minimal protein interaction interface on WWC1/2/3 that can robustly and specifically activate LATS1/2 has been identified. This research uncovers the molecular mechanism of LATS1/2 regulation and provides a strategy for treating various malignancies related to Hippo pathway dysregulation.
Article
Multidisciplinary Sciences
Shuaifeng Li, Shixun Han, Qi Zhang, Yibing Zhu, Haitao Zhang, Junli Wang, Yang Zhao, Jianhui Zhao, Lin Su, Li Li, Dawang Zhou, Cunqi Ye, Xin-Hua Feng, Tingbo Liang, Bin Zhao
Summary: The study reveals that elevated FUNDC2 causes mitochondrial fragmentation through inhibiting MFN1 in hepatocellular carcinoma. The findings suggest FUNDC2 as a potential therapeutic target for liver cancer.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Qi-tao Chen, Zhi-yuan Zhang, Qiao-ling Huang, Hang-zi Chen, Wen-bin Hong, Tianwei Lin, Wen-xiu Zhao, Xiao-min Wang, Cui-yu Ju, Liu-zheng Wu, Ya-ying Huang, Pei-pei Hou, Wei-jia Wang, Dawang Zhou, Xianming Deng, Qiao Wu
Summary: In response to TGF-beta stimulation, hepatic stellate cells secrete HK1 via large extracellular vesicles. The released HK1 is taken up by hepatocellular carcinoma cells, promoting tumor progression and metastasis.