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      Altered decorin expression of systemic sclerosis by UVA1 (340–400 nm) phototherapy: Immunohistochemical analysis of 3 cases

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      1 , , 1 , 1
      BMC Dermatology
      BioMed Central

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          Abstract

          Background

          Ultraviolet A1 (340–400 nm, UVA1) phototherapy is highly effective in sclerotic lesions of systemic sclerosis (SSc). Histological evaluation of skin specimens obtained before and after UVA1 phototherapy revealed loosening of collagen bundles and the appearance of small collagen fibers. We have previously shown that UVA1 irradiation induced collagenase in vitro study by using SSc fibroblasts. The increased levels of mRNA and protein of decorin in SSc fibroblasts were reported. In this study, we focus on the lesional expression of small dermatan sulfate proteoglycan, decorin that has a role of binding to collagen and fibrillogenesis.

          Case presentation

          We employed immunohistochemical analysis of decorin before and after UVA1 phototherapy. The skin specimens from three patients who were effectively treated with UVA1 phototherapy were analysed. Monoclonal antibody 6B6 as the specific reactivity to decorin was used. The increased decorin was focally accumulated in the newly synthesized collagen fibers in the sclerotic lesion of SSc. After UVA1 phototherapy, decorin was decreased in upper to middle dermis, although decorin was slightly increased in papillary dermis.

          Conclusions

          These results suggest that decreased and normalized levels of accumulated decorin may relate to the efficacy of sclerotic lesions in UVA1 phototherapy.

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          Most cited references19

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          Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease.

          The central pathological feature of human kidney disease that leads to kidney failure is the accumulation of extracellular matrix in glomeruli. Overexpression of transforming growth factor-beta (TGF-beta) underlies the accumulation of pathological matrix in experimental glomerulonephritis. Administration of an antibody raised against TGF-beta to glomerulonephritic rats suppresses glomerular matrix production and prevents matrix accumulation in the injured glomeruli. One of the matrix components induced by TGF-beta, the proteoglycan decorin, can bind TGF-beta and neutralize its biological activity, so decorin may be a natural regulator of TGF-beta (refs 3, 4). We tested whether decorin could antagonize the action of TGF-beta in vivo using the experimental glomerulonephritis model. We report here that administration of decorin inhibits the increased production of extracellular matrix and attenuates manifestations of disease, confirming our hypothesis. On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-beta.
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            The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins.

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              • Record: found
              • Abstract: found
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              Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor.

              Decorin, a small leucine-rich proteoglycan, is capable of suppressing the growth of various tumor cell lines when expressed ectopically. In this report, we investigated the biochemical mechanism by which decorin inhibits cell cycle progression. In A431 squamous carcinoma cells, decorin proteoglycan or protein core induced a marked growth suppression, when either exogenously added or endogenously produced by a transgene. Decorin caused rapid phosphorylation of the EGF receptor and a concurrent activation of mitogen-activated protein (MAP) kinase signal pathway. This led to a protracted induction of endogenous p21, a potent inhibitor of cyclin-dependent kinases, and ultimate cell cycle arrest. Biglycan, a related proteoglycan, had no effect. Moreover, decorin activated the EGF receptor/MAP kinase/ p21 axis in cell lines of various histogenetic backgrounds. These results provide the first evidence that EGF and decorin converge functionally to regulate the cell cycle through activation of a common pathway which ultimately leads to growth suppression.
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                Author and article information

                Journal
                BMC Dermatol
                BMC Dermatology
                BioMed Central (London )
                1471-5945
                2003
                12 March 2003
                : 3
                : 2
                Affiliations
                [1 ]Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
                Article
                1471-5945-3-2
                10.1186/1471-5945-3-2
                153525
                12689342
                57290a0f-6a48-42bb-9a87-cc63373b8014
                Copyright © 2003 Sawada et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
                History
                : 12 December 2002
                : 12 March 2003
                Categories
                Case Report

                Dermatology
                Dermatology

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