Changes in elastin, elastin binding protein and versican in alveoli in chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>COPD is characterised by loss of alveolar elastic fibers and by lack of effective repair. Elastic fibers are assembled at cell surfaces by elastin binding protein (EBP), a molecular chaperone whose function can be reversibility inhibited by chondroitin sulphate of matrix proteoglycans such as versican. This study aimed to determine if alveoli of patients with mild to moderate COPD contained increased amounts of versican and a corresponding decrease in EBP, and if these changes were correlated with decreases in elastin and FEV₁.</p> <p>Methods</p> <p>Lung samples were obtained from 26 control (FEV₁≥ 80% predicted, FEV₁/VC >0.7) and 17 COPD patients (FEV₁≥ 40% – <80% predicted, FEV₁/VC ≤ 0.7) who had undergone a lobectomy for bronchial carcinoma. Samples were processed for histological and immuno-staining. Volume fractions (<it>V</it>_v) of elastin in alveolar walls and alveolar rims were determined by point counting, and versican and EBP assessed by grading of staining intensities.</p> <p>Results</p> <p>Elastin <it>V</it>v was positively correlated with FEV₁for both the alveolar walls (r = 0.66, p < 0.001) and rims (r = 0.41, p < 0.01). Versican was negatively correlated with FEV₁in both regions (r = 0.30 and 0.32 respectively, p < 0.05), with the highest staining intensities found in patients with the lowest values for FEV₁. Conversely, staining intensities for EBP in alveolar walls and rims and were positively correlated with FEV₁(r = 0.43 and 0.46, p < 0.01).</p> <p>Conclusion</p> <p>Patients with mild to moderate COPD show progressively increased immuno-staining for versican and correspondingly decreased immuno-staining for EBP, with decreasing values of FEV₁. These findings may explain the lack of repair of elastic fibers in the lungs of patients with moderate COPD. Removal of versican may offer a strategy for effective repair.</p

Altered fibroblast proteoglycan production in COPD

<p>Abstract</p> <p>Background</p> <p>Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production.</p> <p>Methods</p> <p>Proliferation, proteoglycan production and the response to TGF-β₁were examined <it>in vitro </it>in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV) and from control subjects.</p> <p>Results</p> <p>Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma. Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p < 0.01). In addition, perlecan production was lower in centrally derived fibroblasts from COPD patients than from control subjects (p < 0.01). TGF-β₁triggered similar increases in proteoglycan production in distally derived fibroblasts from COPD patients and control subjects. In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-β₁than those from control subjects.</p> <p>Conclusions</p> <p>The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development. Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil. In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD.</p

Stakeholder engagement in the city branding process

This paper explores perceptions of stakeholder engagement in the city branding process from the perspective of two post-industrial cities: Sheffield, UK and Essen, Germany. This qualitative research utilises a multi case study approach, which allowed for semi-structure interviews and semiotics to be used. Preliminary findings highlight that there are four stakeholder ‘levels’. Each of these stakeholder groupings is involved in the city branding process to some extend. Findings suggest that the degree of involvement strongly depends on the primary stakeholders, who are seen as key decision-makers in the branding process. These primary stakeholders select other stakeholders that ‘can’ be involved in the branding process. Although this may be beneficial it is vital to provide more opportunities and incorporate stakeholders that are willing to participate in the branding process. Alienating stakeholders may also lead to losing parts of an identity that is based on heritage. The focus is on two cities with a highly industrialised background, thus findings may not be applicable to cities without this heritage. The paper looks at both stakeholder engagement and city branding, thereby proposing four layers of stakeholder involvement in the city branding process

Dairy products and total calcium intake at 13 years of age and its association with obesity at 21 years of age

Background/objectives: Dairy products and specifically calcium have been suggested to play a role in obesity development but more longitudinal evidence is still needed. The objective of this study was to assess the association between dairy products and total calcium intake at age 13 and body mass index at age 21. Subjects/methods: This longitudinal study included 2159 individuals from the Epidemiological Health Investigation of Teenagers cohort (EPITeen), Porto, Portugal, evaluated at ages 13 and 21. Assessment consisted of anthropometrics measurements and structured questionnaires namely a semi-quantitative food frequency questionnaire to appraise food consumption in the past 12 months. Linear regression models were run in 941 individuals with complete information of confounders: gender, follow-up period, parents’ education, physical activity, energy, and total calcium intake. Results: Negative association was found on total calcium intake at age 13 with BMI at age 21 (model 0: β = −0.059 (95% CI: −0.113, −0.004) and model 1: −0.057 (95% CI: −0.113, −0.002)), however, no statistically significant association was found when adjusting for energy intake (model 2: β = −0.031 (95% CI: −0.110, 0.047). There were no associations between milk, yogurt, and cheese consumption at age 13 and BMI at age 21 when adjusting for confounders. Conclusions: This study did not support an independent effect of dairy products or total calcium intake in adolescence on later early adulthood adiposity.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01-0145-FEDER-016829), under the project MetHyOS (Ref. FCT PTDC/DTP-EPI/6506/2014) and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). Also this study was developed with the support of the research teams of the Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine of Porto University; the EPIUnit—Public Health Institute of Porto University; and the EPITeen Cohort Study

Endogenous laminin is required for human airway smooth muscle cell maturation

BACKGROUND: Airway smooth muscle (ASM) contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM) components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. METHODS: Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. RESULTS: Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP) significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. CONCLUSION: While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the first time that endogenously expressed laminin is required for ASM maturation to the contractile phenotype. As endogenously expressed laminin chains α2, β1 and γ1 are uniquely increased during myocyte maturation, these laminin chains may be key in this process. Thus, human ASM maturation appears to involve regulated endogenous expression of a select set of laminin chains that are essential for accumulation of contractile phenotype myocytes

Strategisches Handeln von Startups im Kontext der Mediatisierung

Junge Gründer und Start-ups müssen sich in einer schnell wandelnden und mediatisierten Wettbewerbsumwelt behaupten. Ihr Handeln wird geprägt von sozialen Netzwerkmedien wie Facebook, LinkedIn oder Instagram. Um auf diesen Medien-plattformen erfolgreich zu sein, müssen Markenführung und Markenkommunikation strategisch verankert sein. Der Aufsatz präsentiert daher eine qualitative Analyse empirischer Daten aus dem Kontext des Start-up-Incubator neudeli der Bauhaus-Universität Weimar und verdeutlicht, dass die Mediatisierung grundlegend in die strategische Entwicklung der Marke von jungen Gründern und Start-ups eingreift. Die Studie verdeutlicht das Verständnis strategischer Markenführung in mediatisierten Kontexten und zeigt, dass drei idealtypische Praktiken zur Markenführung und strategischen Entwicklung beitragen: 1) Bürokratische Medienarbeit, 2) Mediale Kreativarbeit, 3) Netzwerkarbeit durch Medien