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      MicroRNA-222 regulates the viability of fibroblasts in hypertrophic scars via matrix metalloproteinase 1

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          Abstract

          The present study aimed to determine the expression of microRNA (miR)-222 in hypertrophic scar (HS) tissues, and investigate the regulatory mechanism of miR-222 in HS. A total of 36 patients diagnosed with HS between August 2013 and May 2016 were included in the present study. HS tissues and HS-adjacent tissues were collected from patients. Primary fibroblasts were obtained from HS tissue. Reverse transcription-quantitative polymerase chain reaction was used to measure mRNA levels of matrix metalloproteinase 1 (MMP1) and miR-222. Western blotting was conducted to determine MMP1 expression and an MTT assay was performed to measure the viability of fibroblasts. A dual luciferase reporter assay was used to identify the binding of miR-222 to MMP1 mRNA. It was demonstrated that MMP1 serves a role in HS at the transcription level and that increased MMP1 expression inhibited the viability of fibroblasts. miR-222 serves a regulatory role in HS by targeting its target gene MMP1 and regulates the expression of MMP1 by binding to its 3′-untranslated region. The decreased expression of miR-222 suppresses the viability of fibroblasts by regulating MMP1 expression. The present study demonstrated that the downregulation of MMP1 in HS tissues is associated with the upregulation of miR-222 expression. miR-222 may therefore regulate the viability of fibroblasts in HS and the expression of related proteins via MMP1.

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          Most cited references34

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          Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages

          Cancer secreted exosomal miRNAs are emerging as mediators between tumor-stoma crosstalk. Here, we show epithelial ovarian cancer (EOC)-derived exosomes activated macrophages to a tumor-associated macrophage (TAM)-like phenotype with SOCS3/STAT3 pathway involvement, which could facilitate the progression of cancer. MiR-222-3p was enrichment in exosomes released from EOC cells and it could be transferred to macrophages. Overexpression of miR-222-3p in macrophages induced polarization of the M2 phenotype. Luciferase assay verified miR-222-3p targeted SOCS3 genes and expression of SOCS3 was decreased after transfection with a miR-222-3p mimic. Down-regulation of SOCS3 correlated with an increased expression of STAT3 activation. MiR-222-3p could be detected in the exosomes from serum and its levels were related to EOC. These observations propose tumor-derived exosomal miR-222-3p is an effective regulator in the polarization of tumor-promoting M2 macrophages and may be a biomarker of EOC.
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            On the nature of hypertrophic scars and keloids: a review.

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              Hypertrophic scars and keloids--a review of their pathophysiology, risk factors, and therapeutic management.

              Hypertrophic scars and keloids result from an abnormal fibrous wound healing process in which tissue repair and regeneration-regulating mechanism control is lost. These abnormal fibrous growths present a major therapeutic dilemma and challenge to the plastic surgeon because they are disfiguring and frequently recur. To provide updated clinical and experimental information on hypertrophic scars and keloids so that physicians can better understand and properly treat such lesions. A Medline literature search was performed for relevant publications and for diverse strategies for management of hypertrophic scars and keloids. The growing understanding of the molecular processes of normal and abnormal wound healing is promising for discovery of novel approaches for the management of hypertrophic scars and keloids. Although optimal treatment of these lesions remains undefined, successful healing can be achieved only with combined multidisciplinary therapeutic regimens.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                February 2018
                14 December 2017
                14 December 2017
                : 15
                : 2
                : 1803-1808
                Affiliations
                [1 ]Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
                [2 ]Department of Dermatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
                [3 ]Department of Surgery Lab, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
                Author notes
                Correspondence to: Dr Kang Zeng, Department of Dermatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Road, Guangzhou, Guangdong 510515, P.R. China, E-mail: ycv888@ 123456126.com
                Article
                ETM-0-0-5634
                10.3892/etm.2017.5634
                5776557
                29434768
                c2078bc1-6cec-405e-9471-44cc519b8545
                Copyright: © Zhang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 17 September 2016
                : 10 April 2017
                Categories
                Articles

                Medicine
                hypertrophic scar,microrna-222,matrix metallopro-teinase 1
                Medicine
                hypertrophic scar, microrna-222, matrix metallopro-teinase 1

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