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      Role of Transforming Growth Factor- β1 and Smads Signaling Pathway in Intrauterine Adhesion

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          Abstract

          The aim of the study was to evaluate the role of Smad3, Smad7, and TGF- β1 in intrauterine adhesion (IUA) patients and experimental rabbit models. 60 IUA patients, 30 control participants, and 18 female rabbits were enrolled in this study. We found that the plasma concentrations and protein expressions of TGF- β1 were significantly increased in patients and experimental rabbits compared to those in controls ( P < 0.05). Furthermore, the mRNA and protein expression levels of Smad3 were significantly elevated, while Smad7 level was markedly decreased in the patients and experimental rabbits compared with controls ( P < 0.05). This altered ratio recommended that IUA was positively correlated to the mRNA and protein expression levels of Smad3, Smad7, and TGF- β1 in blood and uterine tissue. Moreover, we used the specific inhibitor of Smad3 (SIS3) in experimental rabbit. SIS3 obviously reduced the mRNA and protein expression of smad3 and TGF- β1, while it increased Smad7 expression in the treatment groups as compared with IUA rabbits ( P < 0.05). Our study suggested that TGF- β1/Smad3/smad7 is a major pathway which plays an important role in the regulation of the IUA and specific inhibitor of Smad3 (SIS3) may provide a new therapeutic strategy for IUA.

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          Most cited references54

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          TGF-beta signal transduction.

          The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.
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            Making sense of latent TGFbeta activation.

            TGFbeta is secreted as part of a latent complex that is targeted to the extracellular matrix. A variety of molecules, 'TGFbeta activators,' release TGFbeta from its latent state. The unusual temporal discontinuity of TGFbeta synthesis and action and the panoply of TGFbeta effects contribute to the interest in TGF-beta. However, the logical connections between TGFbeta synthesis, storage and action are obscure. We consider the latent TGFbeta complex as an extracellular sensor in which the TGFbeta propeptide functions as the detector, latent-TGFbeta-binding protein (LTBP) functions as the localizer, and TGF-beta functions as the effector. Such a view provides a logical continuity for various aspects of TGFbeta biology and allows us to appreciate TGFbeta biology from a new perspective.
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              Transcriptional control by the TGF-beta/Smad signaling system.

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                Author and article information

                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi Publishing Corporation
                0962-9351
                1466-1861
                2016
                21 February 2016
                : 2016
                : 4158287
                Affiliations
                1Department of Gynecology, Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, China
                2Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China
                3Department of OB/GYN, Baylor College of Medicine, 6651 Main Street, 10th Floor, Houston, TX 77030, USA
                4Center for Medical Experiments, Third Xiangya Hospital, Central South University, Changsha, Hunan, China
                Author notes

                Academic Editor: Marc Pouliot

                Article
                10.1155/2016/4158287
                4779532
                26997760
                500c0346-ed97-4e73-9cb5-dcf074f5b061
                Copyright © 2016 Umme Salma et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 November 2015
                : 19 January 2016
                : 26 January 2016
                Categories
                Research Article

                Immunology
                Immunology

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