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      Urinary Peptidomic Biomarkers in Kidney Diseases

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          Abstract

          In order to effectively develop personalized medicine for kidney diseases we urgently need to develop highly accurate biomarkers for use in the clinic, since current biomarkers of kidney damage (changes in serum creatinine and/or urine albumin excretion) apply to a later stage of disease, lack accuracy, and are not connected with molecular pathophysiology. Analysis of urine peptide content (urinary peptidomics) has emerged as one of the most attractive areas in disease biomarker discovery. Urinary peptidome analysis allows the detection of short and long-term physiological or pathological changes occurring within the kidney. Urinary peptidomics has been applied extensively for several years now in renal patients, and may greatly improve kidney disease management by supporting earlier and more accurate detection, prognostic assessment, and prediction of response to treatment. It also promises better understanding of kidney disease pathophysiology, and has been proposed as a “liquid biopsy” to discriminate various types of renal disorders. Furthermore, proteins being the major drug targets, peptidome analysis may allow one to evaluate the effects of therapies at the protein signaling pathway level. We here review the most recent findings on urinary peptidomics in the setting of the most common kidney diseases.

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          Cellular and molecular mechanisms in kidney fibrosis.

          Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution.
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            Data integration in the era of omics: current and future challenges

            To integrate heterogeneous and large omics data constitutes not only a conceptual challenge but a practical hurdle in the daily analysis of omics data. With the rise of novel omics technologies and through large-scale consortia projects, biological systems are being further investigated at an unprecedented scale generating heterogeneous and often large data sets. These data-sets encourage researchers to develop novel data integration methodologies. In this introduction we review the definition and characterize current efforts on data integration in the life sciences. We have used a web-survey to assess current research projects on data-integration to tap into the views, needs and challenges as currently perceived by parts of the research community.
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              The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis?

              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.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                21 December 2019
                January 2020
                : 21
                : 1
                : 96
                Affiliations
                [1 ]Nephrology and Dialysis Unit, Department of Medicine, G. d’Annunzio University, Chieti-Pescara, SS.Annunziata Hospital, Via dei Vestini, 66013 Chieti, Italy; vittorio.sirolli@ 123456unich.it (V.S.); lorenzo.diliberato@ 123456asl2abruzzo.it (L.D.L.)
                [2 ]Proteomics and Metabonomics Unit, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy; l.pieroni@ 123456hsantalucia.it
                [3 ]Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
                [4 ]Department of Laboratory Diagnostic and Infectious Diseases, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
                Author notes
                Author information
                https://orcid.org/0000-0001-7141-1817
                https://orcid.org/0000-0002-8466-6314
                Article
                ijms-21-00096
                10.3390/ijms21010096
                6982248
                31877774
                5dc003d5-c8fc-4f0c-82fd-60ba89028470
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 November 2019
                : 19 December 2019
                Categories
                Review

                Molecular biology
                kidney,urine,peptidomics,biomarker,ckd,clinical proteomics,mass spectrometry
                Molecular biology
                kidney, urine, peptidomics, biomarker, ckd, clinical proteomics, mass spectrometry

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