Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis—a serological evaluation

Leeming, Diana Julie; Byrjalsen, I.; Jiménez, Wladimiro; Christiansen, Claus; Karsdal, Morten A.

doi:10.1111/liv.12044

Cited by 51 publications

(39 citation statements)

References 35 publications

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“…Other functions of this network are the provision of interaction sites for other ECM components, inflammatory cells, chemokines, cytokines, and important functions in cellular signaling (394). The collagen formation observed during fibrosis is also accompanied by an increase in type IV collagen degradation and unfavorable remodeling of the basement membranes, resulting from an increased expression of proteases in the affected tissue (129,194,351). This favors myofibroblast activation and a net increase in the deposition of, for example, fibrillar collagens by myofibroblasts (379).…”

Section: Fibrosis and The Ecmmentioning

confidence: 99%

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

Karsdal

Manon‐Jensen

Genovese

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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222

176

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Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases.collagen; cytokine; extracellular fibrogenesis; integrin; laminin; matrix metalloproteinase; posttranslational modification; proteoglycan; endocrine 45% OF ALL DEATHS IN THE DEVELOPED WORLD are associated with chronic fibroproliferative diseases (256, 378). Thus there is an increasing need to address fibroproliferative diseases because of their strong impact on the quality of life and health costs consequent to pain and organ failure, with an increased need for organ transplants despite dwindling availability, often followed by death. Moreover, their severity and perceived irreversibility in view of a current paucity of treatment options, coupled with a high prevalence in most and an orphan status in some fibrotic diseases, have just begun to attract biotechnology and big pharmaceutical companies to the field.The common denominator of fibroproliferative diseases is a dysregulated tissue remodeling leading to the excessive and abnormal accumulation of extracellular matrix (ECM) components, thereby generating an ECM with different structural and signaling properties in the affected tissues (285, 287, 289, 378 -380). Fibrosis can affect almost any organ or tissue and is therefore associated with a wide variety of diseases and injuries (287). Figure 1 illustrates the major fibroproliferative diseases with a significant impact on human health (20, ...

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Section: Fibrosis and The Ecmmentioning

confidence: 99%

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

Karsdal

Manon‐Jensen

Genovese

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

222

176

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“…The role of biglycan in fibrosis may be tissue specific since biglycan does not affect TGF-␤-induced pulmonary fibrosis (186), and biglycan mRNA appears not to be increased in mercuric chlorideinduced renal tubulointerstitial fibrosis (350). However, biglycan expression and serological levels of its processed byproducts correlate with the extent of liver fibrosis in murine models (108,204). Biglycan is also involved with progression and poor prognosis in a variety of malignancies such as gastrointestinal and endometrial cancers (7,122,221,377,415).…”

Section: Proteoglycansmentioning

confidence: 99%

“…In addition, Col-VI spiked some attention due to its selective expression in some fibrotic conditions (i.e., kidney and myocardial fibrosis) as well as in hepatocellular carcinoma (136). In fact, its level of expression has been recently proposed to serve as a clinical prognostic marker (204,205). Carcinomas that typically present an aggressive progression (i.e., liver and pancreas) are characterized by a large deposition of interstitial FN and collagen.…”

Section: Collagenmentioning

confidence: 99%

The wound healing, chronic fibrosis, and cancer progression triad

Rybinski

Franco‐Barraza

Cukierman

2014

Physiological Genomics

215

175

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For decades tumors have been recognized as “wounds that do not heal.” Besides the commonalities that tumors and wounded tissues share, the process of wound healing also portrays similar characteristics with chronic fibrosis. In this review, we suggest a tight interrelationship, which is governed as a concurrence of cellular and microenvironmental reactivity among wound healing, chronic fibrosis, and cancer development/progression (i.e., the WHFC triad). It is clear that the same cell types, as well as soluble and matrix elements that drive wound healing (including regeneration) via distinct signaling pathways, also fuel chronic fibrosis and tumor progression. Hence, here we review the relationship between fibrosis and cancer through the lens of wound healing.

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“…Among these methods, ELISA for the neo-epitope of the 7S domain (P4NP 7S) and that of the α3 chain (C4M12a3) have been applied to evaluate liver fibrosis in animal models. However, the usefulness of these assays to investigate pathological remodeling in human chronic liver diseases including NAFLD has not been validated [29][30][31]. Future clinical studies are required to establish the significance of these novel fibrosis markers in NAFLD.…”

Section: Discussionmentioning

confidence: 99%

“…Assessment of basement membrane remodeling using monoclonal antibodies against neo-epitopes released in serum after the degradation of type IV collagen by matrix metalloproteinase has recently become possible. As novel markers of fibrosis, the serum levels of specific fragments of type IV collagen have been measured by competitive ELISAs [29][30][31]. These fibrosis markers are theoretically more reliable than others, because fibrosis is characterized by excessive basement membrane remodeling; furthermore, remodeling by matrix metalloproteinase generates neo-epitopes released into the circulation.…”

Section: Discussionmentioning

confidence: 99%

Serum Immunoreactive Collagen IV detected by Monoclonal Antibodies as a Marker of Severe Fibrosis in Patients with Non- Alcoholic Fatty Liver Disease

Aida

Abe

Tomita

et al. 2015

JGLD

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Background & Aims: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We evaluated serum collagen IV as a direct non-invasive marker of severe liver fibrosis in NAFLD.Methods: The study included 148 NAFLD and 187 chronic hepatitis C patients in whom histological severity of liver fibrosis was evaluated. The utility of serum collagen IV measured by immune-mediated agglutination using two types of monoclonal antibodies for distinguishing severe fibrosis (≥ stage 3 and ≥ F3) from non-to-moderate fibrosis in NAFLD or chronic hepatitis C was assessed in comparison to serum hyaluronic acid or other indirect fibrosis markers.Results: Multiple logistic regression analysis showed that serum collagen IV was significantly associated with severe fibrosis in NAFLD (odds ratio: 1.21, p<0.001) but not in chronic hepatitis C. For distinguishing severe fibrosis in NAFLD, collagen IV showed the largest area under the receiver-operating characteristic curve (0.827, 95%CI: 0.746-0.908) followed by FIB-4 (0.805, 95%CI: 0.728-0.890); in chronic hepatitis C, those for FIB-4 (0.813, 95%CI: 0.748-0.878) and collagen IV (0.770, 95%CI: 0.683-0.857) were the largest and smallest, respectively. To detect severe fibrosis in NAFLD, a cutoff of collagen IV > 177 exhibited 77.1% sensitivity, 84.0% specificity, 76.5% positive predictive value, and 84.0% negative predictive value. Combined with a cutoff of FIB-4 > 2.09, the negative and positive predictive values, and specificity for detecting severe fibrosis in NAFLD increased further.Conclusion: Collagen IV is a reliable marker for distinguishing severe liver fibrosis from non-to-moderate fibrosis in NAFLD but not chronic hepatitis C.

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Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis—a serological evaluation

Abstract: As the markers can be used for translational science, these markers may provide valuable information for the evaluation of liver fibrosis in clinical settings.

Cited by 51 publications

References 35 publications

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

The wound healing, chronic fibrosis, and cancer progression triad

Serum Immunoreactive Collagen IV detected by Monoclonal Antibodies as a Marker of Severe Fibrosis in Patients with Non- Alcoholic Fatty Liver Disease

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