Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis

Sepúlveda‐Crespo, Daniel; Resino, Salvador; Martı́nez, Isidoro

doi:10.1007/s40265-020-01458-x

Cited by 14 publications

(11 citation statements)

References 327 publications

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“…Among the cell types, macrophages play an important role in the two-way regulation of liver fibrosis, while NK cells have a wide range of pathogen and activated cell clearance functions. 42 , 43 The specific immune cells are mainly T cells, which play an important role in the occurrence of anti-infective immunity, anti-tumor immunity, and autoimmune diseases. T cells cooperate with IL-17 to inhibit liver inflammation, but whether T cells can block the formation and mechanism underlying liver fibrosis remains to be studied.…”

Section: Mechanisms Underlying Hepatic Fibrosis and Ppar-γmentioning

confidence: 99%

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

Li¹,

Guo²,

Wu³

2021

DDDT

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Liver fibrosis is a common link in the transformation of acute and chronic liver diseases to cirrhosis. It is of great clinical significance to study the factors associated with the induction of liver fibrosis and elucidate the method of reversal. Peroxisome proliferator-activated receptors (PPARs) are a class of nuclear transcription factors that can be activated by peroxisome proliferators. PPARs play an important role in fibrosis of various organs, especially the liver, by regulating downstream targeted pathways, such as TGF-β, MAPKs, and NF-κB p65. In recent years, the development and screening of PPAR-γ ligands have become a focus of research. The PPAR-γ ligands include synthetic hypolipidemic and antidiabetic drugs. In addition, microRNAs, lncRNAs, circRNAs and nano new drugs have attracted research interest. In this paper, the research progress of PPAR-γ in the pathogenesis and treatment of liver fibrosis was discussed based on the relevant literature in recent years.

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Section: Mechanisms Underlying Hepatic Fibrosis and Ppar-γmentioning

confidence: 99%

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

Li¹,

Guo²,

Wu³

2021

DDDT

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“…Liver cirrhosis can also promote the development of hepatocellular carcinoma (HCC) [ 4 ]. Accurately diagnosing early stages of liver fibrosis is essential for disease management, due to the reversibility of fibrosis through the removal/treatment of the cause of injury [ 5 , 6 , 7 ]. A leading cause of liver damage involves the intake of drugs, known as drug-induced liver injury (DILI), which is a major challenge in clinical medicine and drug development [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of miR-199a-5p, miR-214-3p and miR-99b-5p as Fibrosis-Specific Extracellular Biomarkers and Promoters of HSC Activation

Messner

Schmidt

Özkul

et al. 2021

IJMS

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Liver fibrosis is characterized by the accumulation of extracellular matrix (ECM) resulting in the formation of fibrous scars. In the clinic, liver biopsies are the standard diagnostic method despite the potential for clinical complications. miRNAs are single-stranded, non-coding RNAs that can be detected in tissues, body fluids and cultured cells. The regulation of many miRNAs has been linked to tissue damage, including liver fibrosis in patients, resulting in aberrant miRNA expression/release. Experimental evidence also suggests that miRNAs are regulated in a similar manner in vitro and could thus serve as translational in vitro–in vivo biomarkers. In this work, we set out to identify and characterize biomarkers for liver fibrosis that could be used in vitro and clinically for research and diagnostic purposes. We focused on miRNAs released from hepatic 3D cultures exposed to methotrexate (MTX), which causes fibrosis, and acetaminophen (APAP), an acute hepatotoxicant with no clinically relevant association to liver fibrosis. Using a 3D in vitro model, we corroborated compound-specific responses as we show MTX induced a fibrotic response, and APAP did not. Performing miRNA-seq of cell culture supernatants, we identified potential miRNA biomarkers (miR-199a-5p, miR-214-3p, niRNA-125a-5p and miR-99b-5p) that were associated with a fibrotic phenotype and not with hepatocellular damage alone. Moreover, transfection of HSC with miR-199a-5p led to decreased expression of caveolin-1 and increased α-SMA expression, suggesting its role in HSC activation. In conclusion, we propose that extracellular miR-214-3p, miR-99b-5p, miR-125a-5p and specifically miR-199a-5p could contribute towards a panel of miRNAs for identifying liver fibrosis and that miR-199a-5p, miR-214-3p and miR-99b-5p are promoters of HSC activation.

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“…92,93 Meanwhile, hepatocytes and cholangiocytes damage exposes the liver in an inflammatory environment which indirectly promotes liver fibrosis. 94,95 Notably, current studies on the changes of ACE2 and TMPRSS2 under hypoxia are controversial. Activated hypoxiainducible factor 1α (HIF-1α) inhibits ACE2 expression under mild hypoxia, which may represent a novel approach to respond to COVID-19 through hypoxia conditioning, however, severe hypoxiainduced upregulation of HIF-1α will trigger a life-threatening cytokine storm.…”

Section: Ace2 Receptor and Cytopathymentioning

confidence: 99%

“…Despite ACE2 is hardly expressed in inactivated HSC, it is upregulated after Ang Ⅱ stimulation, indicating its closely association with HSC activation, liver fibrosis and the susceptibility of CLD patients to SARS‐CoV‐2 92,93 . Meanwhile, hepatocytes and cholangiocytes damage exposes the liver in an inflammatory environment which indirectly promotes liver fibrosis 94,95 . Notably, current studies on the changes of ACE2 and TMPRSS2 under hypoxia are controversial.…”

Section: Pathological Mechanism Of Liver Injury Under Covid‐19mentioning

confidence: 99%

COVID‐19‐associated liver injury: Adding fuel to the flame

Wang,

Shen,

et al. 2023

Cell Biochemistry & Function

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COVID‐19 is mainly characterized by respiratory disorders and progresses to multiple organ involvement in severe cases. With expansion of COVID‐19 and SARS‐CoV‐2 research, correlative liver injury has been revealed. It is speculated that COVID‐19 patients exhibited abnormal liver function, as previously observed in the SARS and MERS pandemics. Furthermore, patients with underlying diseases such as chronic liver disease are more susceptible to SARS‐CoV‐2 and indicate a poor prognosis accompanied by respiratory symptoms, systemic inflammation, or metabolic diseases. Therefore, COVID‐19 has the potential to impair liver function, while individuals with preexisting liver disease suffer from much worse infected conditions. COVID‐19 related liver injury may be owing to direct cytopathic effect, immune dysfunction, gut−liver axis interaction, and inappropriate medication use. However, discussions on these issues are infancy. Expanding research have revealed that angiotensin converting enzyme 2 (ACE2) expression mediated the combination of virus and target cells, iron metabolism participated in the virus life cycle and the fate of target cells, and amino acid metabolism regulated immune response in the host cells, which are all closely related to liver health. Further exploration holds great significance in elucidating the pathogenesis, facilitating drug development, and advancing clinical treatment of COVID‐19‐related liver injury. This article provides a review of the clinical and laboratory hepatic characteristics in COVID‐19 patients, describes the etiology and impact of liver injury, and discusses potential pathophysiological mechanisms.

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Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis

Cited by 14 publications

References 327 publications

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

Identification of miR-199a-5p, miR-214-3p and miR-99b-5p as Fibrosis-Specific Extracellular Biomarkers and Promoters of HSC Activation

COVID‐19‐associated liver injury: Adding fuel to the flame

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