Inhibition of circular RNA ASPH reduces the proliferation and promotes the apoptosis of hepatic stellate cells in hepatic fibrosis

Meng, Hongwu; Jiang, Lingfeng; Jia, Peng-cheng; Niu, Ruowen; Bu, Fang-tian; Zhu, Yan; Pan, Xue‐Yin; Li, Juanjuan; Liu, Jinyu; Zhang, Yilong; Huang, Cheng; Lv, Xiongwen; Li, Jun

doi:10.1016/j.bcp.2023.115451

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…137 CircASPH was upregulated in LF, and downregulation of circASPH suppressed HSCs activation and hepatic fibrogenesis via the circASPH/miR-139-5p/Notch1 axis. 138 ncRNAs that regulate genes in signaling pathways involved in histone modifications during HSCs fibrogenic activation are presented in Table 3.…”

Section: Circular Rnasmentioning

confidence: 99%

Mechanisms of Epigenetic Regulation in the Fibrogenic Activation of Hepatic Stellate Cells in Non-alcoholic Fatty Liver Disease

Garbuzenko

2024

Gene Expr

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Non-alcoholic fatty liver disease (NAFLD) is an extremely prevalent disease, and the presence and severity of liver fibrosis are considered one of the most important factors determining its prognosis. Hepatic stellate cells (HSCs) are essential in hepatic fibrogenesis associated with NAFLD. A number of factors underlying NAFLD pathogenesis may promote HSCs activation, leading to the development of profibrotic and proinflammatory signs. In addition, for the fibrogenic transdifferentiation of quiescent HSCs, alterations in multiple genes are necessary, where epigenetic regulation plays a defining role. Epigenetic regulation induces changes in gene activity without altering the coding sequence, and these changes are stably inherited after the factor causing the alteration has disappeared. Epigenetic modifications comprise several regulatory mechanisms, including DNA methylation, covalent histone modification, chromatin remodeling, and non-coding RNAs. Since the mechanisms underlying epigenetic regulation of HSCs fibrogenic activation are reversible and dynamic, molecular targeted therapies aimed at correcting these mechanisms provide promising prospects for novel therapeutic approaches for treating liver fibrosis

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Section: Circular Rnasmentioning

confidence: 99%

Mechanisms of Epigenetic Regulation in the Fibrogenic Activation of Hepatic Stellate Cells in Non-alcoholic Fatty Liver Disease

Garbuzenko

2024

Gene Expr

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“…For example, the treatment of siRNA silencing CCR2 can regulate liver immune to inhibit the infiltration of profibrotic macrophages and neutrophils in murine fibrotic livers[ 137 ]. Another study showed that circRNA ASPH regulated liver fibrosis by binding miR-139-5p by regulating neurogenic locus notch homolog protein 1 (Notch 1) expression[ 138 ].…”

Section: Current Treatment Options For Liver Fibrosismentioning

confidence: 99%

Treatment of liver fibrosis: Past, current, and future

Zhang¹,

Liu²,

Yang³

2023

World J Hepatol

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Liver fibrosis accompanies the progression of chronic liver diseases independent of etiologies, such as hepatitis viral infection, alcohol consumption, and metabolic-associated fatty liver disease. It is commonly associated with liver injury, inflammation, and cell death. Liver fibrosis is characterized by abnormal accumulation of extracellular matrix components that are expressed by liver myofibroblasts such as collagens and alpha-smooth actin proteins. Activated hepatic stellate cells contribute to the major population of myofibroblasts. Many treatments for liver fibrosis have been investigated in clinical trials, including dietary supplementation ( e.g. , vitamin C), biological treatment ( e.g. , simtuzumab), drug ( e.g. , pegbelfermin and natural herbs), genetic regulation ( e.g. , non-coding RNAs), and transplantation of stem cells ( e.g. , hematopoietic stem cells). However, none of these treatments has been approved by Food and Drug Administration. The treatment efficacy can be evaluated by histological staining methods, imaging methods, and serum biomarkers, as well as fibrosis scoring systems, such as fibrosis-4 index, aspartate aminotransferase to platelet ratio, and non-alcoholic fatty liver disease fibrosis score. Furthermore, the reverse of liver fibrosis is slowly and frequently impossible for advanced fibrosis or cirrhosis. To avoid the life-threatening stage of liver fibrosis, anti-fibrotic treatments, especially for combined behavior prevention, biological treatment, drugs or herb medicines, and dietary regulation are needed. This review summarizes the past studies and current and future treatments for liver fibrosis.

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“…The primary mechanism through which AHWE had this impact was by preventing HSC activation and proliferation [87]. The inhibition of circASPH, which is derived from the aspartate β-hydroxylase (ASPH) gene locus, can suppress the activation and proliferation of HSCs, while its upregulation promoted the occurrence of these events in a CCl 4 -induced mouse model of liver fibrosis [88]. CircDIDO1 (death-inducer obliterator 1) inhibits HSC activation by inhibiting the Akt pathway, and overexpression of circDIDO1 can induce cell cycle arrest and inhibit HSC proliferation and activation in the human HSC cell line LX-2 [89].…”

Section: Limitation Of Hsc Activationmentioning

confidence: 99%

Liver Fibrosis Resolution: From Molecular Mechanisms to Therapeutic Opportunities

Pei,

Yi,

Tang

2023

IJMS

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The liver is a critical system for metabolism in human beings, which plays an essential role in an abundance of physiological processes and is vulnerable to endogenous or exogenous injuries. After the damage to the liver, a type of aberrant wound healing response known as liver fibrosis may happen, which can result in an excessive accumulation of extracellular matrix (ECM) and then cause cirrhosis or hepatocellular carcinoma (HCC), seriously endangering human health and causing a great economic burden. However, few effective anti-fibrotic medications are clinically available to treat liver fibrosis. The most efficient approach to liver fibrosis prevention and treatment currently is to eliminate its causes, but this approach’s efficiency is too slow, or some causes cannot be fully eliminated, which causes liver fibrosis to worsen. In cases of advanced fibrosis, the only available treatment is liver transplantation. Therefore, new treatments or therapeutic agents need to be explored to stop the further development of early liver fibrosis or to reverse the fibrosis process to achieve liver fibrosis resolution. Understanding the mechanisms that lead to the development of liver fibrosis is necessary to find new therapeutic targets and drugs. The complex process of liver fibrosis is regulated by a variety of cells and cytokines, among which hepatic stellate cells (HSCs) are the essential cells, and their continued activation will lead to further progression of liver fibrosis. It has been found that inhibiting HSC activation, or inducing apoptosis, and inactivating activated hepatic stellate cells (aHSCs) can reverse fibrosis and thus achieve liver fibrosis regression. Hence, this review will concentrate on how HSCs become activated during liver fibrosis, including intercellular interactions and related signaling pathways, as well as targeting HSCs or liver fibrosis signaling pathways to achieve the resolution of liver fibrosis. Finally, new therapeutic compounds targeting liver fibrosis are summarized to provide more options for the therapy of liver fibrosis.

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Inhibition of circular RNA ASPH reduces the proliferation and promotes the apoptosis of hepatic stellate cells in hepatic fibrosis

Cited by 5 publications

References 54 publications

Mechanisms of Epigenetic Regulation in the Fibrogenic Activation of Hepatic Stellate Cells in Non-alcoholic Fatty Liver Disease

Mechanisms of Epigenetic Regulation in the Fibrogenic Activation of Hepatic Stellate Cells in Non-alcoholic Fatty Liver Disease

Treatment of liver fibrosis: Past, current, and future

Liver Fibrosis Resolution: From Molecular Mechanisms to Therapeutic Opportunities

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