Analysis of Plasma Tenascin-C in Post-HCV Cirrhosis: A Prospective Study

Benbow, Jennifer H.; Elam, April; Bossi, Krista; Massengill, Danae L.; Brandon-Warner, Elizabeth; Anderson, William E.; Culberson, Cathy; Russo, Mark W.; deLemos, Andrew S.; Schrum, Laura W.

doi:10.1007/s10620-017-4860-z

Cited by 7 publications

(4 citation statements)

References 36 publications

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“…Tenascin-C upregulation was detected in a rat model of liver fibrosis induced by CCl 4 ( 238 ), probably produced by HSCs ( 368 ) and in the livers of patients with liver cirrhosis, HCC and chronic HCV, where it correlates with progressive disease activity ( 82 , 83 , 84 , 85 ). Plasma levels of tenascin-C, together with AST, also provide an effective model to discriminate HCV cirrhotic patients with active infection from healthy controls and patients with undetectable levels of HCV RNA post HCV treatment regimen, highlighting tenascin-C as a potential indicator of ongoing hepatic injury and inflammation in these patients ( 369 ).…”

Section: Ecm Proteins With Both Pro- and Anti-inflammatory Effects Onmentioning

confidence: 99%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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Chronic liver disease when accompanied by underlying fibrosis, is characterized by an accumulation of extracellular matrix (ECM) proteins and chronic inflammation. Although traditionally considered as a passive and largely architectural structure, the ECM is now being recognized as a source of potent damage-associated molecular pattern (DAMP)s with immune-active peptides and domains. In parallel, the ECM anchors a range of cytokines, chemokines and growth factors, all of which are capable of modulating immune responses. A growing body of evidence shows that ECM proteins themselves are capable of modulating immunity either directly via ligation with immune cell receptors including integrins and TLRs, or indirectly through release of immunoactive molecules such as cytokines which are stored within the ECM structure. Notably, ECM deposition and remodeling during injury and fibrosis can result in release or formation of ECM-DAMPs within the tissue, which can promote local inflammatory immune response and chemotactic immune cell recruitment and inflammation. It is well described that the ECM and immune response are interlinked and mutually participate in driving fibrosis, although their precise interactions in the context of chronic liver disease are poorly understood. This review aims to describe the known pro-/anti-inflammatory and fibrogenic properties of ECM proteins and DAMPs, with particular reference to the immunomodulatory properties of the ECM in the context of chronic liver disease. Finally, we discuss the importance of developing novel biotechnological platforms based on decellularized ECM-scaffolds, which provide opportunities to directly explore liver ECM-immune cell interactions in greater detail.

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Section: Ecm Proteins With Both Pro- and Anti-inflammatory Effects Onmentioning

confidence: 99%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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“…In contrast, mild respiratory infections, including the common cold viruses respiratory syncytial virus (RSV) and human parainfluenza virus, do not lead to the upregulation of tenascin-C levels ( 54 ). Beyond respiratory tract infections, tenascin-C has also been proposed as a biomarker of chronic hepatitis C infection, as it has been found to be elevated in serum and histological liver samples correlating with active infection, cirrhosis, and tissue injury ( 55 , 56 ), as well as liver fibrosis status ( 57 ).…”

Section: Tenascin-c As a Biomarker Of Disease Severity During Covid-1...mentioning

confidence: 99%

A virological view of tenascin-C in infection

Zuliani-Alvarez

Piccinini

2023

American Journal of Physiology-Cell Physiology

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Tenascin-C is a large extracellular matrix glycoprotein with complex, not yet fully unveiled roles. Its context- and structure-dependent modus operandi renders tenascin-C a puzzling protein. Since its discovery ~40 years ago, research into tenascin-C biology continues to reveal novel functions, the most recent of all being its immunomodulatory activity, especially its role in infection, which is just now beginning to emerge. Here, we explore the role for tenascin-C in the immune response to viruses, including SARS-CoV-2 and HIV-1. Recently, tenascin-C has emerged as a biomarker of disease severity during COVID-19 and other viral infections and we highlight relevant RNA-Seq and proteomic analyses that suggest a correlation between tenascin-C levels and disease severity. Finally, we ask what the function of this protein during viral replication is and propose tenascin-C as an intercellular signal of inflammation shuttled to distal sites via exosomes, a player in the repair and remodeling of infected and damaged tissues during severe infectious disease as well as a ligand for specific pathogens with distinct implications for the host.

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“…A chronic liver injury leads to the activation of HSCs, with concomitant enhanced secretion of tenascin-C in chronic hepatitis C [ 104 ]. Serum tenascin-C has therefore been suggested as a biomarker to discriminate between fibrotic/cirrhotic patients with active hepatitis C from healthy controls and those with HCV eradication after antiviral therapy [ 105 ]. Tenascin-C serum levels were found to be good indicators of ongoing hepatic injury and inflammation in fibrotic/cirrhotic patients.…”

Section: Liver Fibrosis and Cirrhosismentioning

confidence: 99%

“…Tenascin-C serum levels were found to be good indicators of ongoing hepatic injury and inflammation in fibrotic/cirrhotic patients. After SVR, serum levels of this protein returned to the baseline observed in healthy individuals, suggesting the reversion of HSCs to their quiescent state [ 105 ]. More specifically, serum levels of large splice variants of tenascin-C were proposed as useful markers of the inflammatory activity during chronic hepatitis C and in particular of the degree of piecemeal necrosis [ 167 ].…”

Section: Liver Fibrosis and Cirrhosismentioning

confidence: 99%

Molecular Crosstalk between the Hepatitis C Virus and the Extracellular Matrix in Liver Fibrogenesis and Early Carcinogenesis

Reungoat

Grigorov

Zoulim

et al. 2021

Cancers

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Chronic infection by the hepatitis C virus (HCV) is a major cause of liver diseases, predisposing to fibrosis and hepatocellular carcinoma. Liver fibrosis is characterized by an overly abundant accumulation of components of the hepatic extracellular matrix, such as collagen and elastin, with consequences on the properties of this microenvironment and cancer initiation and growth. This review will provide an update on mechanistic concepts of HCV-related liver fibrosis/cirrhosis and early stages of carcinogenesis, with a dissection of the molecular details of the crosstalk during disease progression between hepatocytes, the extracellular matrix, and hepatic stellate cells.

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Analysis of Plasma Tenascin-C in Post-HCV Cirrhosis: A Prospective Study

Abstract: TnC and AST provided the best model for discriminating HCV cirrhotics with active infection from HC and virologic cure cohorts over current liver injury markers, suggesting TnC as a potential indicator of ongoing hepatic injury and inflammation.

Cited by 7 publications

References 36 publications

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

A virological view of tenascin-C in infection

Molecular Crosstalk between the Hepatitis C Virus and the Extracellular Matrix in Liver Fibrogenesis and Early Carcinogenesis

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