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      Decorin is a pivotal effector in the extracellular matrix and tumour microenvironment

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          Abstract

          Decorin (DCN), an extracellular matrix (ECM) protein, belongs to the small leucine-rich proteoglycan family. As a pluripotent molecule, DCN regulates the bioactivities of cell growth factors and participates in ECM assembly. Accumulating evidence has shown that DCN acts as a ligand of various cytokines and growth factors by directly or indirectly interacting with the corresponding signalling molecules involved in cell growth, differentiation, proliferation, adhesion and metastasis and that DCN especially plays vital roles in cancer cell proliferation, spread, pro-inflammatory processes and anti-fibrillogenesis. The multifunctional nature of DCN thus enables it to be a potential therapeutic agent for a variety of diseases and shows good prospects for clinical and research applications.

          DCN, an extracellular matrix (ECM) protein that belongs to the small leucine-rich proteoglycan family, is widely distributed and plays multifunctional roles in the stroma and epithelial cells. Originally, DCN was known as an effective collagen-binding partner for fibrillogenesis [ 1] and to modulate key biomechanical parameters of tissue integrity in the tendon, skin and cornea [ 2]; thus, it was named decorin (DCN). Since being initially cloned in 1986, DCN was discovered to be a structural constituent of the ECM [ 3]. However, the paradigm has been shifted; it has become increasingly evident that in addition to being a matrix structural protein, DCN affects a wide range of biological processes, including cell growth, differentiation, proliferation, adhesion, spread and migration, and regulates inflammation and fibrillogenesis [ 47]. Two main themes for DCN functions have emerged: maintenance of cellular structure and regulation of signal transduction pathways, culminating in anti-tumourigenic effects. Here, we review the interaction network of DCN and emphasize the biological correlations between these interactions, some of which are expected to be therapeutic intervention targets.

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          Negative regulation of transforming growth factor-beta by the proteoglycan decorin.

          Decorin is a small chondroitin-dermatan sulphate proteoglycan consisting of a core protein and a single glycosaminoglycan chain. Eighty per cent of the core protein consists of 10 repeats of a leucin-rich sequence of 24 amino acids. Similar repeats have been found in two other proteoglycans, biglycan and fibromodulin, and in several other proteins including Drosophila morphogenetic proteins. Expression of high levels of decorin in Chinese hamster ovary cells has a dramatic effect on their morphology and growth properties. We now report that this effect is due at least in part to the ability of decorin to bind transforming growth factor-beta, an autocrine factor that stimulates the growth of Chinese hamster ovary cells. As transforming growth factor-beta induces synthesis of decorin in many cell types, our results suggest that decorin may be a component of a feedback system regulating cell growth.
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            Origin of myofibroblasts and cellular events triggering fibrosis.

            Renal fibrosis is a major hallmark of chronic kidney disease that is considered to be a common end point of various types of renal disease. To date, the biological meaning of fibrosis during the progression of chronic kidney diseases is unknown and possibly depends on the cell type contributing to extracellular matrix production. During the past decade, the origin of myofibroblasts in the kidney has been intensively investigated. Determining the origins of renal myofibroblasts is important because these might account for the heterogeneous characteristics and behaviors of myofibroblasts. Current data strongly suggest that collagen-producing myofibroblasts in the kidney can be derived from various cellular sources. Resident renal fibroblasts and cells of hematopoietic origin migrating into the kidney seem to be the most important ancestors of myofibroblasts. It is likely that both cell types communicate with each other and also with other cell types in the kidney. In this review, we will discuss the current knowledge on the origin of scar-producing myofibroblasts and cellular events triggering fibrosis.
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              The regulatory roles of small leucine-rich proteoglycans in extracellular matrix assembly.

              Small leucine-rich proteoglycans (SLRPs) are involved in a variety of biological and pathological processes. This review focuses on their regulatory roles in matrix assembly. SLRPs have protein cores and hypervariable glycosylation with multivalent binding abilities. During development, differential interactions of SLRPs with other molecules result in tissue-specific spatial and temporal distributions. The changing expression patterns play a critical role in the regulation of tissue-specific matrix assembly and therefore tissue function. SLRPs play significant structural roles within extracellular matrices. In addition, they play regulatory roles in collagen fibril growth, fibril organization and extracellular matrix assembly. Moreover, they are involved in mediating cell-matrix interactions. Abnormal SLRP expression and/or structures result in dysfunctional extracellular matrices and pathophysiology. Altered expression of SLRPs has been found in many disease models, and structural deficiency also causes altered matrix assembly. SLRPs regulate assembly of the extracellular matrix, which defines the microenvironment, modulating both the extracellular matrix and cellular functions, with an impact on tissue function. © 2013 The Authors Journal compilation © 2013 FEBS.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                12 January 2018
                3 January 2018
                : 9
                : 4
                : 5480-5491
                Affiliations
                1 Cancer Institute, Xuzhou Medical University, Xuzhou, China
                2 Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
                3 Jiangsu Center for The Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China
                Author notes
                Correspondence to: Junnian Zheng, fl@ 123456xzhmu.edu.cn
                Article
                23869
                10.18632/oncotarget.23869
                5797066
                29435195
                f0cd77ff-27e5-4339-967c-5019e0eab7d3
                Copyright: © 2018 Zhang et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 21 July 2017
                : 27 December 2017
                Categories
                Review

                Oncology & Radiotherapy
                anti-fibrosis,anti-tumour,decorin,pro-inflammatory,proteoglycan
                Oncology & Radiotherapy
                anti-fibrosis, anti-tumour, decorin, pro-inflammatory, proteoglycan

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