No abstract

No abstract

Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease (CKD) leading to kidney failure. The clinical course of many renal diseases, and thereby of CKD, is highly variable. One of the major challenges in deciding which treatment approach is best suited for a patient but also in the development of new treatments is the lack of markers able to identify and stratify patients with stable versus progressive disease. At the moment renal biopsy is the only means of diagnosing renal interstitial fibrosis. Novel biomarkers should improve diagnosis of a disease, estimate its prognosis and assess the response to treatment, all in a non-invasive manner. Existing markers of CKD do not fully and specifically address these requirements and in particular do not specifically reflect renal fibrosis. The aim of this review is to give an insight of the involvement of the extracellular matrix (ECM) proteins in kidney diseases and as a source of potential novel biomarkers of renal fibrosis. In particular the use of the protein fingerprint technology, that identifies neo-epitopes of ECM proteins generated by proteolytic cleavage by proteases or other post-translational modifications, might identify such novel biomarkers of renal fibrosis.

No abstract

PRO-C3 is an independent predictor of fibrosis stage in NAFLD. A PRO-C3 based score (ADAPT) accurately identifies patients with NAFLD and advanced fibrosis and is superior to APRI, FIB-4 and NFS. This article is protected by copyright. All rights reserved.

No abstract

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, ...

No abstract