| 1. |
- Andersson Sjöland, Annika, et al.
(författare)
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Versican in inflammation and tissue remodelling: the impact on lung disorders.
- 2015
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 25:3, s. 243-251
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Forskningsöversikt (refereegranskat)abstract
- Versican is a proteoglycan that has many different roles in tissue homeostasis and inflammation. The biochemical structure is comprised of four different types of the core protein with attached glycosaminoglycans that can be sulphated to various extents and has the capacity to regulate differentiation of different cell types, migration, cell adhesion, proliferation, tissue stabilization and inflammation. Versican's regulatory properties are of importance during both homeostasis and changes that lead to disease progression. The glycosaminoglycans that are attached to the core protein are of the chondroitin sulfate/dermatan sulfate type and are known to be important in inflammation through interactions with cytokines and growth factors. For a more complex understanding of versican it is of importance to study the tissue niche, where the wound healing process in both healthy and diseased conditions take place. In previous studies our group has identified changes in the amount of the multifaceted versican in chronic lung disorders such as asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome, which could be a result of pathologic, transforming growth factor β driven, on-going remodelling processes. Reversely, the context of versican in its niche is of great importance since versican has been reported to have a beneficial role in other contexts e.g. emphysema. Here we explore the vast mechanisms of versican in healthy lung and in lung disorders.
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| 2. |
- Brooke, Hannah L, et al.
(författare)
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Adult children's socioeconomic resources and mothers' survival after a breast cancer diagnosis : a Swedish population-based cohort study.
- 2017
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Socioeconomic inequalities in survival after breast cancer persist worldwide. We aim to determine whether adult offspring's socioeconomic resources contribute to inequalities in mothers' survival after breast cancer.METHODS: 14 231 women, aged 65-79 years, with a child aged ≥30 years and a first primary diagnosis of breast cancer in the National Cancer Register between 2001 and 2010 were followed until death, 10 years after diagnosis, or end of study (December 2015). Relative survival proportions and excess mortality within 10 years of diagnosis by strata of offspring's education level and disposable income were estimated using flexible parametric models accounting for measures of mothers' socioeconomic position and expected mortality in the general population.RESULTS: 4292 women died during 102 236 person-years of follow-up. Crude 10-year relative survival proportions for mothers of children with >14, 12-14 and <12 years of education were 0.89 (0.87 to 0.91), 0.87 (0.85 to 0.89) and 0.79 (0.76 to 0.81), respectively. Compared with mothers of children with >14 years of education, mothers of children with <12 or 12-14 years of education had substantially higher excess mortality (excess HR 1.69 (1.38 to 2.07) and 1.22 (1.00 to 1.48), respectively). Higher mortality did not differ between tertiles of offspring's disposable income.CONCLUSIONS: Adult offspring's education level may contribute to inequalities in mothers' survival after breast cancer. Clinicians should be aware of the educational context beyond the individual and women with less educated offsprings may require extra support. This should be considered in future research, policy frameworks and interventions aimed at reducing survival inequalities.
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| 3. |
- Larsson Callerfelt, Anna-Karin, et al.
(författare)
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iNOS affects matrix production in distal lung fibroblasts from patients with mild asthma.
- 2015
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Ingår i: Pulmonary Pharmacology & Therapeutics. - : Elsevier BV. - 1522-9629 .- 1094-5539. ; 34:sep 9, s. 64-71
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Forskningsöversikt (refereegranskat)abstract
- A high level of exhaled nitric oxide (NO) is a marker for inflammation in the airways of asthmatic subjects. However, little is known about how NO and inducible nitric oxides synthase (iNOS) activity may affect remodelling in the distal lung. We hypothesized that there is a link between iNOS and ongoing remodelling processes in the distal lung of mild asthmatics.
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| 4. |
- Weitoft, Maria, et al.
(författare)
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Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry
- 2019
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440. ; 189:12, s. 2358-2365
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Tidskriftsartikel (refereegranskat)abstract
- A proportion of patients with severe asthma (SA) show poor responses to traditional asthma medications; however, it remains unknown why some patients remain persistently symptomatic. Our objective was to explore the use of laser-capture microdissection of specific epithelial structures combined with quantitative data-independent acquisition mass spectrometry to elucidate differences in protein composition in patients with SA with varying symptom control. Unbiased label-free quantitative proteome analyses were performed on laser-capture–microdissected areas of specific epithelial structures from patients with SA with varying degrees of symptom control. A total of 1993 stable SA and 1652 symptomatic SA proteins in normal epithelium and 1458 stable SA and 1647 symptomatic SA proteins in metaplastic epithelium were quantified. When comparing proteome profiles based on symptom control, 33 proteins in patients with stable SA (≥twofold change; P ≤ 0.05) and 13 proteins in patients with persistently symptomatic SA (≥twofold change; P ≤ 0.05) were enriched significantly. When comparing proteome profiles based on epithelial status, 21 proteins in normal epithelium (≥twofold change; P ≤ 0.05) and 6 proteins in metaplastic epithelium (≥twofold change; P ≤ 0.05) were enriched significantly. New treatment strategies are needed for patients with severe asthma and exploratory studies of unbiased nature such as this may help when searching for new mechanisms and potential targets involved in the disease pathology.
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| 5. |
- Weitoft, Maria, et al.
(författare)
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Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions
- 2014
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Whether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung. Methods: Bronchial and transbronchial biopsies from healthy controls, patients with controlled atopic and patients with uncontrolled atopic asthma were processed for immunohistochemical analysis of fibroblasts and extracellular matrix molecules: collagen, versican, biglycan, decorin, fibronectin, EDA-fibronectin, matrix metalloproteinase (MMP)-9 and tissue-inhibitor of matrix metalloproteinase (TIMP)-3. Results: In central airways we found increased percentage areas of versican and decorin in patients with uncontrolled asthma compared to both healthy controls and patients with controlled asthma. Percentage area of biglycan was significantly higher in both central airways and alveolar parenchyma of patients with uncontrolled compared to controlled asthma. Ratios of MMP-9/TIMP-3 were decreased in both uncontrolled and controlled asthma compared to healthy controls. In the alveolar parenchyma, patients with uncontrolled asthma had increased percentage areas of collagen, versican and decorin compared to patients with controlled asthma. Patients with uncontrolled asthma had significantly higher numbers of myofibroblasts in both central airways and alveolar parenchyma compared to patients with controlled asthma. Conclusions: Tissue composition differs, in both central and distal airways, between patients with uncontrolled and controlled asthma on equivalent doses of ICS. This altered structure and possible change in tissue elasticity may lead to abnormal mechanical properties, which could be a factor in the persistent symptoms for patients with uncontrolled asthma.
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| 6. |
- Weitoft, Maria
(författare)
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Extracellular Matrix Alterations in Patients with Different Phenotypes of Asthma.
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AbstractAsthma is a chronic disease that affects approximately 300 million people worldwide, and the prevalence is increasing. It has become clear that asthma is a highly heterogeneous disease, with overlapping symptoms but with diverse immunopathology and clinical phenotypes. Also, a significant proportion of asthma patients have remaining symptoms despite treatment. In addition to different phenotypes, it is thus important to consider asthma control across the severity spectrum. Asthma control is determined by a combination of several factors such as symptoms, changes in lung function, functional ability and quality of life. Although remodeling is now generally accepted as a defining characteristic of asthma, its cause and role in the pathophysiology of asthma needs further elucidating. Chronic inflammation can be a driving force behind remodeling processes, though it is now recognized that inflammation and remodeling can also be two parallel processes independent of each other. Asthma was first considered a disease of the central airways, however there is now little doubt about the importance of small airways and the alveolar compartment in asthma pathology. More research is needed on differentiating pathological backgrounds of the diverse phenotypes of asthma to be able to develop more personalized therapies. The specific aims of the studies presented in this thesis were to:1. Examine if distal inflammation in asthmatics leads to structural alterations also in the alveolar parenchyma. Furthermore, we wanted to investigate whether patients with uncontrolled asthma had a distinct tissue composition compared to patients with controlled asthma.2. Examine the populations of mast cells and if there is a connection between a profibrotic subset of mast cells and collagen composition in central airways and alveolar parenchyma in patients with controlled and uncontrolled asthma.3. Investigate if there is a link between exhaled nitric oxide, inducible nitric oxide synthase and remodeling in the distal airways of patients with mild untreated asthma.4. Evaluate if patchy subepithelial remodeling in patients with severe asthma treated with oral corticosteroids could differentiate patients with sufficient control from those with remaining symptoms.5. Investigate recruitment of circulating fibrocyte subtypes and possible recruitment factors in a human allergen provocation study.We found that the lung matrix composition differs between uncontrolled and controlled asthmatics on equivalent doses of ICS, in both central and distal airways. Proteoglycans, including versican, decorin and biglycan, and collagen was altered, as well as matrix modulators. We also saw changes in number of myofibroblasts.Further, patients with uncontrolled atopic asthma, but not patients with controlled asthma, were found to have an altered pro-fibrotic mast cell phenotype in the alveolar parenchyma that is correlated to alveolar collagen VI deposition.When analyzing the link between NO, NO synthases and remodeling events in asthma, it was found that iNOS is linked to remodeling, with a possibly modulatory role, in the distal lung of patients with mild steroid-naïve asthma.Severe asthma was found to be associated with patchy remodeling and regeneration in the central airways. Also, it is unlikely that the detected remodeling accounts for the differences in asthma control between stable and symptomatic patients with severe asthma. Perhaps the determinants of asthma control should be sought after in small airways or alveolar parenchyma.Finally, we successfully isolated CD45+/lin-/CD115-/CD16-/CD34+/dim/CD11b+ fibrocytes from peripheral blood using FACS.
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| 7. |
- Weitoft, Maria, et al.
(författare)
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Plasma proteome changes linked to late phase response after inhaled allergen challenge in asthmatics
- 2022
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge. Methods: Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models. Results: Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes. Conclusions: Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma.
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