Syndecan-4 is a transmembrane heparan sulfate proteoglycan expressed in a variety of cells, and its heparan sulfate glycosaminoglycan side chains bind to several proteins exhibiting various biological roles. The authors have previously demonstrated syndecan-4′s critical roles in pulmonary inflammation. In the current study, however, its role in pulmonary fibrosis was evaluated. Wild-type and syndecan-4-deficient mice were injected with bleomycin, and several parameters of inflammation and fibrosis were analyzed. The mRNA expression of collagen and α-smooth muscle action (α-SMA) in lung tissues, as well as the histopathological lung fibrosis score and collagen content in lung tissues, were significantly higher in the syndecan-4-deficient mice. However, the total cell count and cell differentiation in bronchoalveolar lavage fluid were equivalent between the wild-type and syndecan-4-deficient mice. Although there was no difference in the TGF-β expression in lung tissues between the wild-type and syndecan-4-deficient mice, significantly more activation of Smad3 in lung tissues was observed in the syndecan-4-deficient mice compared to the wild-type mice. Furthermore, in the in vitro experiments using lung fibroblasts, the co-incubation of syndecan-4 significantly inhibited TGF-β-induced Smad3 activation, collagen and α-SMA upregulation. Moreover, syndecan-4 knock-down by siRNA increased TGF-β-induced Smad3 activation and upregulated collagen and α-SMA expression. These findings showed that syndecan-4 inhibits the development of pulmonary fibrosis, at least in part, through attenuating TGF-β signaling.
Midkine is a low‐molecular‐weight heparin‐binding protein that is strongly expressed mainly in the midgestation period and has various physiological activities such as in development and cell migration. Midkine has been reported to be strongly expressed in cancer cells and in inflammation and repair processes, and to be involved in the pathogenesis of various diseases. However, its role in the lung is poorly understood. In this study, we analyzed the clinical characteristics of idiopathic pulmonary fibrosis patients in relation to midkine expression and used a mouse bleomycin‐induced pulmonary fibrosis model to investigate the role of midkine in pulmonary fibrosis. In the idiopathic pulmonary fibrosis patients, the serum midkine level was significantly higher than in healthy subjects, and midkine levels in the serum and bronchoalveolar lavage (BAL) fluid correlated positively with the percentage of inflammatory cells in the BAL fluid. In wild‐type mice, intratracheal bleomycin administration increased midkine expression in lung tissue. Additionally, compared with wild‐type mice, midkine‐deficient mice showed low expression of both collagen and α‐smooth muscle actin, as well as a low value for the pathological lung fibrosis score after bleomycin administration. Furthermore, the total cell count and lymphocyte percentage in the BAL fluid, as well as TNF‐α and transforming growth factor‐β expression in lung tissue, were significantly lower in the midkine‐deficient mice compared with wild‐type mice. These results suggest that midkine is involved in the development of pulmonary fibrosis by regulating inflammatory cell migration into the lung, and TNF‐α and transforming growth factor‐β expression.
Background: Decorin is a small leucine-rich repeat proteoglycan that plays a critical role in collagen fibrillogenesis, and regulates inflammation, wound healing and angiogenesis. In idiopathic pulmonary fibrosis (IPF), decorin is expressed in fibrotic lesions; furthermore, intratracheal gene transfer of decorin has been demonstrated to inhibit bleomycin-induced pulmonary fibrosis. Although these results suggest the critical role of decorin in pulmonary fibrosis, the role of decorin in the acute exacerbation of idiopathic interstitial pneumonia (AE-IIP) has not been clarified in detail. Thus, the goal of this study was to determine the role of decorin in AE-IIP. Methods: We retrospectively analyzed AE-IIP patients who had been admitted to our hospital. First, serum decorin levels were compared among patients with AE-IIP, patients with stable idiopathic interstitial pneumonia (SD-IIP), and healthy subjects. Next, the relationship between serum decorin levels and clinical parameters was analyzed in AE-IIP patients. Finally, the association between serum decorin levels and prognosis was evaluated in AE-IIP patients. IIP was divided into IPF and non-IPF, according to the published guidelines. Results: The serum decorin levels of AE-IIP patients were significantly lower than those of both healthy subjects and SD-IIP patients. Serum decorin levels were not related with the clinical parameters and prognosis, when all IIP patients were analyzed. In IPF patients, serum decorin levels had a significant correlation with oxygenation, and IPF patients with low serum decorin levels had a significantly higher survival rate than those with high serum decorin levels. Conclusions: Serum decorin levels are a potential prognostic biomarker in AE-IPF.
The H S ratio may provide useful information on predicting future risks of asthma exacerbation, as well as on obstructive neutrophilic airway inflammation as one of the non-Th2 biomarkers, in asthma.
. nova cultivarV era é uma nova cultivar de alface crespa, resistente ao florescimento prematuro induzido por altas temperaturas. Em ensaios conduzidos nas principais regiões produtoras de alface do estado de São Paulo (Mogi das Cruzes, Campinas, Ibiúna, etc), durante os meses de verão de 1995/96 e de 1996/97, 'Vera' teve performance consistentemente superior à das cultivares tradicionalmente cultivadas na região, Grand Rapid e Verônica. ORIGEM'Vera' foi selecionadas através do método genealógico, a partir do cruzamento entre as cultivares Verônica e Slow Bolting. Os trabalhos de avaliação e seleção das melhores linhagens e, de plantas dentro das linhagens, foram conduzidos nas Estações Experimentais de Bragança Paulista-SP e de Petrolina-PE, DELLA VECCHIA, P.T.; KOCH, P.S.; KIKUCHI, M. Vera: Nova cultivar de alface crespa resistente ao florescimento prematuro. Horticultura Brasileira, Brasília, v. 17, n.2, p. 171, julho 1999. VERA: Nova cultivar de alface crespa resistente ao florescimento prematuro.Paulo T. Della Vecchia; Paulo S. Koch; Masami Kikuchi Agroflora S.A., C. Postal 427, 12.900-000 Bragança Paulista -SP. RESUMOVera é uma nova cultivar de alface crespa resistente ao florescimento prematuro selecionada através do método genealógico a partir do cruzamento entre as cultivares Verônica e Slow Bolting. 'Vera' corresponde à multiplicação, em escala comercial, da linhagem F 10 AF 470. Em ensaios conduzidos no período de verão nas principais regiões produtoras do estado de São Paulo (Mogi das Cruzes, Campinas, Ibiúna, etc) o início da emissão da haste floral em Vera foi retardado em quinze a vinte dias quando comparado ao da cultivar Grand Rapid e em cinco a sete dias quando comparado ao da cultivar Verônica. Vera is a new cultivar of crisp loose leaf type lettuce resistant to bolting. It was obtained through pedigree selection from the cross between cultivars Verônica and Slow Bolting. Vera corresponds to the commercial increase of the F 10 breeding line AF 470. Based on summer trials carried out in the main production areas of São Paulo state (Mogi das Cruzes, Campinas, Ibiuna, etc) bolting in Vera was delayed by fifteen to twenty days when compared to the cultivar Grand Rapid and by five to seven days when compared to cultivar Verônica. Palavras Keywords: Lactuca sativa L., bolting, resistance.(Aceito para publicação em 08 de março de 1999) durante o período de 1989 a 1996. 'Vera' corresponde à multiplicação, em escala comercial, da linhagem F 10 AF 470. DESCRIÇÃO'Vera' apresenta plantas vigorosas com folhas crespas, bem mais acentuadas do que as da cultivar Verônica, eretas e de coloração verde-clara brilhante, semelhantes às da cultivar Grand Rapid. Suas folhas basais são, em média, 2 a 3 cm mais curtas e 2 a 4 cm mais largas do que as da cv.Verônica. 'Vera' apresenta, em média, menor número de folhas (2 a 3 folhas) do que a cultivar Verônica. Seu ciclo, da semeadura ao ponto ideal de colheita para o mercado, varia de 50 a 70 dias conforme a região e época de cultivo. 'Vera' apresenta excelente resis...
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