Article
Chemistry, Multidisciplinary
Hao Shen, Han Yu, Qian-yu Li, Ya-ting Wei, Jing Fu, Hui Dong, Dan Cao, Lin-na Guo, Lei Chen, Yuan Yang, Ying Xu, Meng-chao Wu, Hong-yang Wang, Yao Chen
Summary: Non-alcoholic fatty liver disease (NAFLD) is a prevalent risk factor for hepatocellular carcinoma (HCC). The progression from NAFLD to HCC involves paracrine communication among hepatic cells. Vascular endothelial growth factor A (VEGFA) plays a crucial role in NAFLD and HCC, but its cellular communication in the transition from NAFLD to HCC is still unclear.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Aiting Yang, Xuzhen Yan, Hufeng Xu, Xu Fan, Mengyang Zhang, Tao Huang, Weiyu Li, Wei Chen, Jidong Jia, Hong You
Summary: The deficiency of HSCs-specific Loxl1 can prevent CCl4-induced hepatic fibrosis and reduce fibrosis and inflammation in liver tissue, with ITGA8/FAK/PI3K/AKT/HIF1a being essential for the function and expression of LOXL1. The study suggests novel mechanisms and potential targets for the treatment of fibrosis in the future.
Article
Engineering, Biomedical
Pengkai Wu, Xinping Luo, Meiling Sun, Beicheng Sun, Minjie Sun
Summary: A versatile nanocomplex was developed that improved liver fibrosis therapy by overcoming biological barriers and co-regulating Kupffer cells, extracellular matrix, and hepatic stellate cells.
Article
Gastroenterology & Hepatology
Boyun Shi, Wei Wang, Mengting Ye, Min Liang, Ziyu Yu, Yingying Zhang, Zhaoyu Liu, Xue Liang, Jian Ao, Fengfeng Xu, Guibin Xu, Xianhan Jiang, Xinke Zhou, Leyuan Liu
Summary: In a multivariate analysis, serum levels of spermidine were found to be significantly reduced with the progression of liver fibrosis. Previous studies have shown that spermidine supplementation can help prevent liver fibrosis through MAP1S. This study aimed to explore the potential of spermidine in alleviating or curing already developed liver fibrosis.
LIVER INTERNATIONAL
(2023)
Review
Oncology
Mehak Passi, Stefan Zahler
Summary: Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide, with most cases being associated with chronic liver fibrosis which leads to increased liver tissue stiffness. Changes in tissue stiffness affect mechanical signaling pathways, modulating the progression of HCC-related genes. However, mechanical signaling pathways are still less emphasized in comparison to classical biochemical signaling pathways in our understanding of cancer.
Article
Immunology
Ying Su, Shan Lu, Chenjian Hou, Kehan Ren, Meili Wang, Xiaoli Liu, Shanyu Zhao, Xiuping Liu
Summary: This study demonstrates that metformin has significant therapeutic value in NASH-derived liver fibrosis by inducing apoptosis in HSCs, but does not affect the proliferation of hepatocytes.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yuan-Quan Zhao, Xi-Wen Deng, Guo-Qi Xu, Jie Lin, Hua-Ze Lu, Jie Chen
Summary: Chronic liver disease or repeated damage to hepatocytes leads to hepatic fibrosis, which is characterized by excessive deposition of extracellular matrix proteins and activation of hepatic stellate cells into myofibroblasts. These processes promote the occurrence and development of hepatic fibrosis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Engineering, Biomedical
Zhipeng Li, Fangqing Wang, Yanying Li, Xiaoxue Wang, Qiao Lu, Di Wang, Cuiping Qi, Chenglei Li, Zhaohuan Li, Bo Lian, Guixiang Tian, Zhiqin Gao, Bo Zhang, Jingliang Wu
Summary: Peripheral nerves play a significant role in the tumor microenvironment by activating hepatic stellate cells (HSCs) through substance P (SP), which promotes invasion and metastasis of hepatocellular carcinoma (HCC). A novel approach of blocking the SP-HSCs-HCC axis using CAP/GA-sHA-DOX NPs was proposed to inhibit HCC development omnidirectionally. The nanoparticles efficiently targeted tumor cells and activated HSCs while effectively inhibiting drug resistance and migration, showcasing promising potential for cancer therapy.
Article
Gastroenterology & Hepatology
Xia Xie, Cheng-Yun Dou, Yu Zhou, Quan Zhou, Hai-Bo Tang
Summary: miR-503 regulates HSC activation and hepatic fibrosis through SMAD7, enhancing the TGF-beta/SMAD pathway.
DIGESTIVE DISEASES AND SCIENCES
(2021)
Article
Nutrition & Dietetics
Shimon Reif, Ariel Atias, Mirit Musseri, Nickolay Koroukhov, Regina Golan Gerstl
Summary: This study investigated whether milk-derived extracellular vesicles (MDEs) can regulate the progression of liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs). The results showed that MDEs can enter HSCs in vitro and in vivo, inhibiting their proliferation and regulating their activation.
Review
Cell Biology
Zui Tan, Hongbao Sun, Taixiong Xue, Cailing Gan, Hongyao Liu, Yuting Xie, Yuqin Yao, Tinghong Ye
Summary: Liver fibrosis is a result of abnormal wound repair response caused by chronic liver injuries, potentially leading to severe diseases. The detailed mechanism of reversing liver fibrosis is still unclear, posing a challenge in the development of anti-fibrosis drugs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Engineering, Biomedical
Ishita Jain, Aidan Brougham-Cook, Gregory H. Underhill
Summary: Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis in non-alcoholic fatty liver disease. This study investigated the impact of extracellular matrix (ECM) and substrate stiffness on chromatin accessibility and gene expression in activated primary human HSCs. The findings revealed the cooperative effects of ECM composition and stiffness on the methylation/acetylation of histones, as well as higher chromatin accessibility and enrichment of fibrosis-related genes in HSCs on softer substrates. Furthermore, candidate regulatory factors were identified, and their knockdown demonstrated a reduction in fibrogenic markers in HSCs.
ACTA BIOMATERIALIA
(2023)
Article
Biotechnology & Applied Microbiology
Ho-Joon Lee, Seon Ju Mun, Cho-Rok Jung, Hyun-Mi Kang, Jae-Eun Kwon, Jae-Sung Ryu, Hyo-Suk Ahn, Ok-Seon Kwon, Jiwon Ahn, Kyung-Sik Moon, Myung Jin Son, Kyung-Sook Chung
Summary: This study established and characterized a novel human hepatic stellate cell line (LSC-1) and used it in various three-dimensional co-culture systems with differentiated HepaRG cells. Comparisons with a commercially available HSC line on monolayer culture showed that LSC-1 exhibited upregulation of fibrogenic genes and increased levels of matrix and adhesion proteins. LSC-1 also had positive effects on co-cultured differentiated HepaRG and showed enhanced responsiveness to transforming growth factor beta 1 exposure in 3D spheroid culture.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Pharmacology & Pharmacy
Huaqing Jing, Yingzi Ren, Yue Zhou, Min Xu, Sona Krizkova, Zbynek Heger, Qiang Lu, Siyu Wang, Xiaoyang Liang, Vojtech Adam, Nan Li
Summary: This study developed a new method for treating liver fibrosis by using nanoenzymes loaded with nilotinib to inhibit the activation of hepatic stellate cells and improve the microenvironment of liver fibrosis. It was found that these nanoenzymes effectively eliminated intrahepatic reactive oxygen species, alleviated the hypoxic microenvironment, and promoted collagen depletion. In mouse experiments, the nanoenzymes showed significant antifibrogenic effects without obvious long-term toxicity.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
Ying Su, Chenjian Hou, Meili Wang, Kehan Ren, Danmei Zhou, Xiaoli Liu, Shanyu Zhao, Xiuping Liu
Summary: This study demonstrated that metformin induces mitochondrial fission in HSCs by phosphorylating AMPK/DRP1 (S616), leading to decreased expression of alpha-SMA and collagen. Additionally, metformin inhibits complex I activity, reducing ATP production and suppressing transcription of mitochondrial genes. Upregulation of HK2 and GLUT1 mRNA expression enhances glycolysis, while increased mtDNA copy number inhibits HSCs proliferation and activation. In conclusion, metformin can induce mitochondrial fragmentation and low-level energy metabolism in HSCs, thereby reversing liver fibrosis.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)