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      Different Thymosin Beta 4 Immunoreactivity in Foetal and Adult Gastrointestinal Tract

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          Abstract

          Background

          Thymosin beta 4 (Tβ 4) is a member of beta-thymosins, a family of peptides that play essential roles in many cellular functions. A recent study from our group suggested a role for Tβ 4 in the development of human salivary glands. The aim of this study was to analyze the expression of Tβ 4 in the human gut during development, and in the adult.

          Methodology/Principal Findings

          Immunolocalization of Tβ 4 was studied in autoptic samples of tongue, oesophagus, stomach, ileum, colon, liver and pancreas obtained from two human foetuses and two adults. Tβ 4 appeared unevenly distributed, with marked differences between foetuses and adults. In the stomach, superficial epithelium was positive in foetuses and negative in adults. Ileal enterocytes were strongly positive in the adult and weakly positive in the foetuses. An increase in reactivity for Tβ 4 was observed in superficial colon epithelium of adults as compared with the foetuses. Striking differences were found between foetal and adult liver: the former showed a very low reactivity for Tβ 4 while in the adult we observed a strong reactivity in the vast majority of the hepatocytes. A peculiar pattern was found in the pancreas, with the strongest reactivity observed in foetal and adult islet cells.

          Significance

          Our data show a strong expression of Tβ 4 in the human gut and in endocrine pancreas during development. The observed differential expression of Tβ 4 suggests specific roles of the peptide in the gut of foetuses and adults. The observed heterogeneity of Tβ 4 expression in the foetal life, ranging from a very rare detection in liver cells up to a diffuse reactivity in endocrine pancreas, should be taken into account when the role of Tβ 4 in the development of human embryo is assessed. Future studies are needed to shed light on the link between Tβ 4 and organogenesis.

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          Most cited references28

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          Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization.

          Cardiac failure has a principal underlying aetiology of ischaemic damage arising from vascular insufficiency. Molecules that regulate collateral growth in the ischaemic heart also regulate coronary vasculature formation during embryogenesis. Here we identify thymosin beta4 (Tbeta4) as essential for all aspects of coronary vessel development in mice, and demonstrate that Tbeta4 stimulates significant outgrowth from quiescent adult epicardial explants, restoring pluripotency and triggering differentiation of fibroblasts, smooth muscle cells and endothelial cells. Tbeta4 knockdown in the heart is accompanied by significant reduction in the pro-angiogenic cleavage product N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP). Although injection of AcSDKP was unable to rescue Tbeta4 mutant hearts, it significantly enhanced endothelial cell differentiation from adult epicardially derived precursor cells. This study identifies Tbeta4 and AcSDKP as potent stimulators of coronary vasculogenesis and angiogenesis, and reveals Tbeta4-induced adult epicardial cells as a viable source of vascular progenitors for continued renewal of regressed vessels at low basal level or sustained neovascularization following cardiac injury.
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            The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells.

            After its initial formation the epicardium forms the outermost cell layer of the heart. As a result of an epithelial-to-mesenchymal transformation (EMT) individual cells delaminate from this primitive epicardial epithelium and migrate into the subepicardial space (Pérez-Pomares et al., Dev Dyn 1997; 210:96-105; Histochem J 1998a;30:627-634). Several studies have demonstrated that these epicardially derived cells (EPDCs) subsequently invade myocardial and valvuloseptal tissues (Mikawa and Fischman, Proc Natl Acad Sci USA 1992;89:9504-9508; Mikawa and Gourdie, Dev Biol 1996;174:221-232; Dettman et al., Dev Biol 1998;193:169-181; Gittenberger de Groot et al., Circ Res 1998;82:1043-1052; Manner, Anat Rec 1999;255:212-226; Pérez-Pomares et al., Dev. Biol. 2002b;247:307-326). A subset of EPDCs continue to differentiate in a variety of different cell types (including coronary endothelium, coronary smooth muscle cells (CoSMCs), interstitial fibroblasts, and atrioventricular cushion mesenchymal cells), whereas other EPDCs remain in a more or less undifferentiated state. Based on its specific characteristics, we consider the EPDC as the ultimate 'cardiac stem cell'. In this review we briefly summarize what is known about events that relate to EPDC development and differentiation while at the same time identifying some of the directions where EPDC-related research might lead us in the near future. Copyright 2004 Wiley-Liss, Inc.
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              Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues.

              Here, we review the biochemical and molecular properties of thymosin beta(4) (Tbeta(4)), the major actin-sequestering molecule in eukaryotic cells, and its key role in dermal- and corneal-wound healing. Tbeta(4) has several, novel, potential clinical applications in the repair and remodeling of ulcerated tissues and solid organs following hypoxic injuries, such as myocardial infarction and stroke. It might also have important repair functions in the pathophysiologic sequelae that are associated with actin toxicity and with septic shock, such as respiratory distress syndrome, multi-organ failure and severe tissue trauma.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                9 February 2010
                : 5
                : 2
                : e9111
                Affiliations
                [1 ]Divisione di Anatomia Patologica, Dipartimento di Citomorfologia, University of Cagliari, Cagliari, Italy
                [2 ]Dipartimento di Scienze Applicate ai Biosistemi, Università di Cagliari, Cagliari, Italy
                [3 ]Istituto di Biochimica e di Biochimica Clinica, Università Cattolica and/or Istituto per la Chimica del Riconoscimento Molecolare, CNR, Istituto Scientifico, Internazionale (ISI) Paolo VI, Roma, Italy
                The University of Hong Kong, China
                Author notes

                Conceived and designed the experiments: SN TC FC MUF DF BM IM MC GF. Performed the experiments: SN FC MUF IM MC GF. Analyzed the data: SN TC FC MUF DF BM IM MC GF. Contributed reagents/materials/analysis tools: FC MUF. Wrote the paper: SN TC IM MC GF.

                Article
                09-PONE-RA-13724R1
                10.1371/journal.pone.0009111
                2817748
                20161756
                0611b9ca-103e-477a-81a6-41b5660b6795
                Nemolato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 17 October 2009
                : 12 January 2010
                Page count
                Pages: 6
                Categories
                Research Article
                Developmental Biology/Embryology
                Developmental Biology/Organogenesis
                Developmental Biology/Pattern Formation

                Uncategorized
                Uncategorized

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