Article
Pharmacology & Pharmacy
Junfu Fan, Gaozan Tong, Xixi Chen, Santie Li, Ying Yu, Shunan Zhu, Kunxuan Zhu, Zijing Hu, Yonggan Dong, Rui Chen, Junjie Zhu, Wenjie Gong, Zhicheng Hu, Bin Zhou, Yiming Chen, Litai Jin, Weitao Cong
Summary: CK2 activation is critical for sustaining the activated and fibrogenic phenotype of HSCs by stabilizing SMO. Inactivation of CK2 may be of therapeutic interest for liver fibrotic diseases.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
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.
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
Biochemistry & Molecular Biology
Ji Hye Yang, Sae Kwang Ku, Il Je Cho, Je Hyeon Lee, Chang-Su Na, Sung Hwan Ki
Summary: Neoagarooligosaccharides (NAOs) have protective effects against hepatic fibrosis and inhibit the TGF-beta/Smad signaling pathway. This was validated in in vitro experiments and mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Min Shen, Yujia Li, Yingqian Wang, Jiangjuan Shao, Feng Zhang, Guoping Yin, Anping Chen, Zili Zhang, Shizhong Zheng
Summary: The study reveals that under conditions of ferroptosis, the total levels of m(6)A modification are significantly increased, potentially triggering autophagy activation by stabilizing BECN1 mRNA. YTHDF1, identified as a key m(6)A reader protein, promotes BECN1 mRNA stability and autophagy activation, making it a potential target for HSC ferroptosis.
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
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
Cell Biology
Ye Tao, Tianming Qiu, Xiaofeng Yao, Liping Jiang, Ningning Wang, Jintong Jiang, Xue Jia, Sen Wei, Jingyuan Zhang, Yuhan Zhu, Wenyue Tian, Guang Yang, Xiaofang Liu, Shuang Liu, Yang Ding, Xiance Sun
Summary: Liver fibrosis is a significant global health issue characterized by HSCs activation and collagen deposition, which can be induced by arsenic exposure leading to ROS generation and IRE1α/NOX4 pathway activation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Junyan Yan, Baowei Hu, Wenjie Shi, Xiaoyi Wang, Jiayuan Shen, Yaping Chen, Huarong Huang, Lifang Jin
Summary: In this study, Gli2 was shown to regulate HSC activation and liver fibrosis through TGF-beta signaling. Conditional deletion of Gli2 in HSCs reduced liver fibrosis and HSC activation in a mouse model. Additionally, Gli2 promoted HSC activation by upregulating cyclin expression and TGF-beta signaling activity. These findings support further research on Gli2 inhibition as a potential therapy for slowing liver fibrosis progression in humans.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
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)
Article
Immunology
Ting-Ting Li, Xiao-Wei Su, Lin-Lin Chen, Wan-Nian Zhang, Jun-Ping Zhang, Yan Wang, Wei-Heng Xu
Summary: Hepatic fibrosis is a stage of chronic liver disease that can lead to cirrhosis or liver cancer. The activation of hepatic stellate cells (HSCs) is a crucial event in fibrosis development and inhibiting this activation has been shown to alleviate fibrosis. Roxarsone, an organoarsenic additive used in livestock production, has been found to inhibit HSC activation and improve liver function in a mouse model of fibrosis. These findings suggest that Roxarsone could be a potential treatment for liver fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Engineering, Biomedical
Yanping Li, Ting Zhang, Jinhang Zhang, Qinhui Liu, Qingyi Jia, Wenfei Chen, Qin Tang, Yimin Xiong, Yan Xia, Ying Xu, Li Mo, Yuan Huang, Jinhan He
Summary: A multitask nanoparticle system called CCR was developed to target the Golgi apparatus of activated hepatic stellate cells (HSCs) for liver fibrosis treatment. The CCR nanoparticles specifically recognized and accumulated in the Golgi apparatus by binding to fibronectin and CD44 on activated HSCs. Treatment with CCR nanoparticles loaded with a hedgehog inhibitor effectively suppressed HSC activation and extracellular matrix secretion, inhibiting liver fibrosis progression.
Article
Biochemistry & Molecular Biology
Andleeb Aslam, Nadeem Sheikh, Muhammad Shahzad, Ghazala Saeed, Naz Fatima, Tasleem Akhtar
Summary: This study investigates the effect of quercetin on liver fibrosis by targeting the Hedgehog pathway. The results demonstrate that quercetin can ameliorate hepatic fibrosis by antagonizing the Hedgehog pathway, leading to improved serum biochemical index, antioxidant enzyme activity, and modulation of key mediators involved in Hh signaling and inflammation. These findings suggest that the Hedgehog pathway could be a potential therapeutic target for the treatment of liver fibrosis, and quercetin shows promise as a therapeutic agent.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Lifeng Qin, Jiawu Tan, Xiaoping Lv, Jiqiao Zhang
Summary: This study confirmed the role of hepatic stellate cells (HSCs) autophagy and the MIF/CD74 signaling pathway in the development of liver fibrosis, and demonstrated the potential anti-fibrotic effect of vanillic acid (VA) through in vivo and in vitro experiments.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Toxicology
Roya Solhi, Abbas Sahebghadam Lotfi, Majid Farzaneh, Zahra Farzaneh, Abbas Piryaei, Mustapha Najimi, Mossoud Vosough
Summary: Hepatic stellate cell (HSC) activation is a major cause of liver fibrosis, and this study aimed to establish an in vitro model that can simultaneously simulate hedgehog signaling and endoplasmic reticulum stress. Through observing the activation markers and cell migration capacity of LX-2 cells, it was found that TGF beta significantly up-regulated the gene expression of fibrogenic markers, enhanced GLI-2 and XBP1 protein levels, and decreased cell migration capacity. The study results also suggested that quercetin can reduce the expression of fibrogenic markers and osteopontin in activated HSCs.
TOXICOLOGY IN VITRO
(2022)