| 31. |
- Junker, Johan P E, 1980-, et al.
(författare)
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Mechanical tension stimulates the transdifferentiation of fibroblasts into myofibroblasts in human burn scars
- 2008
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Ingår i: Burns : journal of the International Society for Burn Injuries. - : Elsevier BV. - 1879-1409. ; 34:7, s. 942-6
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Tidskriftsartikel (refereegranskat)abstract
- Scar formation as a result of burn wounds leads to contraction of the formed granulation tissue, which causes both aesthetic and functional impairment for the patient. Currently, the main treatment methods focus on stretching to prevent tissue contraction. The myofibroblasts play a key role in the contraction of granulation tissue during scar formation, but their presence should normally decrease after wound re-epithelialization. In hypertrophic scars the myofibroblasts persist and is believed to cause further hypertrophy. Previous studies have shown that mechanical tension leads to increased myofibroblast numbers in granulation tissue. In order to evaluate the effect mechanical tension as a result of stretching has on the number of myofibroblasts in burn wound scars, an in vitro model was used. This model used human burn scar biopsies which were stretched and examined after 1 and 6 days to evaluate the effect on the number of myofibroblasts. The stretching caused an increase in the number of myofibroblasts after mechanical stimulation. This indicates that mechanical stimulation using stretching induces fibroblast to myofibroblast transdifferentiation, thus underlining the importance of further investigations of optimal methods of this regime for treating burn scars.
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| 32. |
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| 33. |
- Junker, Robert R., et al.
(författare)
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Covariation and phenotypic integration in chemical communication displays : Biosynthetic constraints and eco-evolutionary implications
- 2018
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 220:3, s. 739-749
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Tidskriftsartikel (refereegranskat)abstract
- Chemical communication is ubiquitous. The identification of conserved structural elements in visual and acoustic communication is well established, but comparable information on chemical communication displays (CCDs) is lacking. We assessed the phenotypic integration of CCDs in a meta-analysis to characterize patterns of covariation in CCDs and identified functional or biosynthetically constrained modules. Poorly integrated plant CCDs (i.e. low covariation between scent compounds) support the notion that plants often utilize one or few key compounds to repel antagonists or to attract pollinators and enemies of herbivores. Animal CCDs (mostly insect pheromones) were usually more integrated than those of plants (i.e. stronger covariation), suggesting that animals communicate via fixed proportions among compounds. Both plant and animal CCDs were composed of modules, which are groups of strongly covarying compounds. Biosynthetic similarity of compounds revealed biosynthetic constraints in the covariation patterns of plant CCDs. We provide a novel perspective on chemical communication and a basis for future investigations on structural properties of CCDs. This will facilitate identifying modules and biosynthetic constraints that may affect the outcome of selection and thus provide a predictive framework for evolutionary trajectories of CCDs in plants and animals.
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| 34. |
- Karlsson, Lisa K, et al.
(författare)
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Human Dermal Fibroblasts : A Potential Cell Source for Endothelialization of Vascular Grafts
- 2009
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Ingår i: Annals of Vascular Surgery. - : Elsevier BV. - 0890-5096 .- 1615-5947. ; 23:5, s. 663-674
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently, there has been an intense ongoing search for suitable cell sources for vascular tissue engineering. Previous studies report that cells with multilineage potential have been found within the connective stroma of the skin. In line with this, preliminary data from our group suggest that human dermal fibroblasts have the capacity to alter their phenotype into an endothelial cell-like phenotype in vitro. As a first step in using these cells in vascular tissue engineering, we investigated their ability to form an endothelial cell-like layer on a scaffold in vitro. Furthermore, we studied the possibility of seeding dermal fibroblasts on a scaffold and later commencing with induction toward an endothelial cell-like phenotype. METHODS: Cells cultured in either normal fibroblast medium or endothelial induction medium were seeded on a gelatin-based scaffold. To study the organization of cells, routine staining was performed. Differentiation was confirmed by Western blotting and immunohistochemistry with antibodies directed toward molecules commonly used to identify endothelial cells. RESULTS AND CONCLUSION: Our data support that human dermal fibroblasts differentiated toward endothelial cell-like cells prior to seeding showed histological resemblance to mature endothelial cells, while fibroblasts seeded and later induced into endothelial differentiation grew in multilayer. However, expression of various surface molecules indicative of an endothelial phenotype was seen using both techniques. In conclusion, the results presented in this study indicate that human dermal fibroblasts differentiated toward an endothelial cell-like phenotype may be a novel cell source for endothelialization of vascular grafts.
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| 35. |
- Kiwanuka, Elizabeth, et al.
(författare)
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CCN2 is transiently expressed by keratinocytes during re-epithelialization and regulates keratinocyte migration in vitro by the ras-MEK-ERK signaling pathway
- 2013
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 185:2, s. E109-E119
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Tidskriftsartikel (refereegranskat)abstract
- Background: CCN2 (previously known as connective tissue growth factor) is a multifunctional matricellular protein that has numerous effects on cell life and cell interactions with the connective tissue. Although the importance of CCN2 for the fibrotic process in wound healing has been well studied, the involvement of CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of the present study was to investigate the role of CCN2 in the epidermis during wound healing. Materials and methods: Immunohistochemistry was done on sections from full-thickness porcine wounds. The effect of CCN2 on the migration of cultured human keratinocytes exposed to scratch wounds, the effect on phosphorylation of extracellular signal-related kinases (ERK), and the effect of adding inhibitors to the ERK/ mitogen-activated protein kinase pathway to human keratinocytes were studied. Results: The CCN2 protein was transiently expressed in vivo at the leading keratinocyte edge during re-epithelialization of full-thickness porcine wounds. In vitro, exogenous addition of CCN2 to human keratinocyte cultures regulated keratinocyte migration and resulted in phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated protein kinase counteracted the effect of CCN2 on migration. Conclusions: CCN2 was transiently expressed at the leading keratinocyte edge in vivo. The biologic importance of this was supported in vitro, because CCN2 regulated human keratinocyte migration through activation of the Ras-mitogen-activated protein kinase kinase-ERK signal transduction pathway.
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| 36. |
- Kiwanuka, Elizabeth, et al.
(författare)
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CCN2 promotes keratinocyte adhesion and migration via integrin alpha 5 beta 1
- 2013
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 319:19, s. 2938-2946
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Tidskriftsartikel (refereegranskat)abstract
- Background: CCN2, (a.k.a. connective tissue growth factor and CTGF) has emerged as a regulator of cell migration. While the importance of CCN2 for the fibrotic process in wound healing has been well studied, the effect of CCN2 on keratinocyte function is not well understood. In this study, we investigated the mechanism behind CCN2-driven keratinocyte adhesion and migration. Materials and methods: Adhesion assays were performed by coating wells with 10 mu g/ml fibronectin (FN) or phosphate-buffered saline (PBS). Keratinocytes were seeded in the presence or absence of 200 ng/ml CCN2, 5 mmol/l ethylenediaminetetraacetic acid, 10 mmol/l cations, 500 mu l arginine-glycine-aspartic acid (RGD), 500 mu M arginine-glycine-glutamate-serine (RGES), and 10 mu g/ml anti-integrin blocking antibodies. Migration studies were performed using a modified Boyden chamber assay. Quantitative PCR was used to study the effect of CCN2 on integrin subunit mRNA expression. To block intracellular pathways, keratinocytes were pretreated with 20 mu M PD98059 (MEN-1 inhibitor) or 20 mu M PF573228 (FAN inhibitor) for 60 min prior the addition of CCN2. Western blot was used to measure CCN2, p-ERK1/2, and ERK1/2. Results: CCN2 enhanced keratinocyte adhesion to fibronectin via integrin alpha 5 beta 1. The addition of anti-integrin alpha 5 beta 1 antibodies reduced CCN2-mediated keratinocyte migration. In addition, CCN2 regulated mRNA and protein expression of integrin subunits alpha 5 and beta 1 CCN2 activated the FAK-MAPK signaling pathway, and pretreatment with MEK1-specific inhibitor PD98059 markedly reduced CCN2-induced keratinocyte migration. Conclusions: Our results demonstrate that CCN2 enhances keratinocyte adhesion and migration through integrin alpha 5 beta 1 and activation of the FAK-MAPK signaling cascade.
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| 37. |
- Kiwanuka, Elizabeth, et al.
(författare)
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Comparison of Healing Parameters in Porcine Full-Thickness Wounds Transplanted with Skin Micrografts, Split-Thickness Skin Grafts, and Cultured Keratinocytes
- 2011
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Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515 .- 1879-1190. ; 213:6, s. 728-735
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Transplantation of skin micrografts (MGs), split-thickness skin grafts (STSGs), or cultured autologous keratinocytes (CKs) enhances the healing of large full-thickness wounds. This study compares these methods in a porcine wound model, investigating the utility of micrograft transplantation in skin restoration. STUDY DESIGN: Full-thickness wounds were created on Yorkshire pigs and assigned to one of the following treatment groups: MGs, STSGs, CKs, wet nontransplanted, or dry nontransplanted. Dry wounds were covered with gauze and the other groups' wounds were enclosed in a polyurethane chamber containing saline. Biopsies were collected 6, 12, and 18 days after wounding. Quantitative and qualitative wound healing parameters including macroscopic scar appearance, wound contraction, neoepidermal maturation, rete ridge formation, granulation tissue thickness and width, and scar tissue formation were studied. RESULTS: Transplanted wounds scored lower on the Vancouver Scar Scale compared with nontransplanted wounds, indicating a better healing outcome. All transplanted wounds exhibited significantly lower contraction compared with nontransplanted wounds. Wounds transplanted with either MGs, STSGs, or CKs showed a significant increase in re-epithelialization compared with nontransplanted wounds. Wounds transplanted with MGs or STSGs exhibited improved epidermal healing compared with nongrafted wounds. Furthermore, transplantation with STSGs or MGs led to less scar tissue formation compared with the nontransplanted wounds. No significant impact on scar formation was observed after transplantation of CKs. CONCLUSIONS: Qualitative and quantitative measurements collected from full-thickness porcine wounds show that transplantation of MGs improve wound healing parameters and is comparable to treatment with STSGs.
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| 38. |
- Kiwanuka, Elizabeth, et al.
(författare)
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Connective tissue growth factor enhances keratinocyte adhesion to fibronectin and promotes migration through integrin alpha5/beta1
- 2012
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Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515 .- 1879-1190. ; 215:3, s. S81-S82
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: We have previously shown that connective tissue growth factor (CTGF) promotes keratinocyte migration during re-epithelialization. In this study, we investigated whether the CTGF-driven migration involved integrin alpha-5/beta-1 - the principal ligand for fibronectin (FN).Methods: Adhesions assays were performed by coating wells with 10 ug/mL FN or phosphate buffered saline (PBS). Keratinocytes were seeded in the presence or absence of 200 ng/mL CTGF, 5 mmol/L EDTA, 10 mmol/L Mg2+, 10 ug/mL anti-integrin alpha-5/beta-1-blocking antibody. Chemotaxsis assays were performed using a modified Boyden chamber. Keratinocytes were pre-incubated with alpha-5/beta-1-antibodies or mouse-IgG for 30 minute, and migration in the absence or presence of 200 ng/mL CTGF was measured. Cells were stained and absorbance was measured at 570 nm. A value of 1 was assigned to untreated cells.Results: Cell adhesion increased 1.5 ± 0.3 folds in wells coated with FN compared to PBS. CTGF enhanced cell adhesion 2.1 ± 0.3 folds, while EDTA reduced CTGF mediated cell adhesion to baseline (1.1 ± 0.2). The addition of the divalent cation Mg2+ restored CTGF-induced adhesion, indicating involvement of integrins. Integrin alpha-5/beta-1-blocking antibodies reversed CTGF-enhanced binding (1.1 ± 0.2). Consistent with the cell adhesion data, CTGF-induced migration was reduced to 1.5 ± 0.3 by anti-integrin alpha-5/beta-1 antibodies compared to the 2.0 ± 0.6 fold increase seen with 200 ng/mL CTGF.
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| 39. |
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| 40. |
- Kunst, Anton E, et al.
(författare)
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Occupational class and ischemic heart disease mortality in the United States and 11 European countries.
- 1999
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Ingår i: American Journal of Public Health. - 0090-0036 .- 1541-0048. ; 89, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Twelve countries were compared with respect to occupational class differences in ischemic heart disease mortality in order to identify factors that are associated with smaller or larger mortality differences. METHODS: Data on mortality by occupational class among men aged 30 to 64 years were obtained from national longitudinal or cross-sectional studies for the 1980s. A common occupational class scheme was applied to most countries. Potential effects of the main data problems were evaluated quantitatively. RESULTS: A north-south contrast existed within Europe. In England and Wales, Ireland, and Nordic countries, manual classes had higher mortality rates than nonmanual classes. In France, Switzerland, and Mediterranean countries, manual classes had mortality rates as low as, or lower than, those among nonmanual classes. Compared with Northern Europe, mortality differences in the United States were smaller (among men aged 30-44 years) or about as large (among men aged 45-64 years). CONCLUSIONS: The results underline the highly variable nature of socioeconomic inequalities in ischemic heart disease mortality. These inequalities appear to be highly sensitive to social gradients in behavioral risk factors. These risk factor gradients are determined by cultural as well as socioeconomic developments.
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