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- Elowsson Rendin, Linda, et al.
(författare)
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Matrisome Properties of Scaffolds Direct Fibroblasts in Idiopathic Pulmonary Fibrosis
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:16
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Tidskriftsartikel (refereegranskat)abstract
- In idiopathic pulmonary fibrosis (IPF) structural properties of the extracellular matrix (ECM) are altered and influence cellular responses through cell-matrix interactions. Scaffolds (decellularized tissue) derived from subpleural healthy and IPF lungs were examined regarding biomechanical properties and ECM composition of proteins (the matrisome). Scaffolds were repopulated with healthy fibroblasts cultured under static stretch with heavy isotope amino acids (SILAC), to examine newly synthesized proteins over time. IPF scaffolds were characterized by increased tissue density, stiffness, ultimate force, and differential expressions of matrisome proteins compared to healthy scaffolds. Collagens, proteoglycans, and ECM glycoproteins were increased in IPF scaffolds, however while specific basement membrane (BM) proteins such as laminins and collagen IV were decreased, nidogen-2 was also increased. Findings were confirmed with histology, clearly showing a disorganized BM. Fibroblasts produced scaffold-specific proteins mimicking preexisting scaffold composition, where 11 out of 20 BM proteins were differentially expressed, along with increased periostin and proteoglycans production. We demonstrate how matrisome changes affect fibroblast activity using novel approaches to study temporal differences, where IPF scaffolds support a disorganized BM and upregulation of disease-associated proteins. These matrix-directed cellular responses emphasize the IPF matrisome and specifically the BM components as important factors for disease progression.
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| 2. |
- Lystedt, Erika, 1978-, et al.
(författare)
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Subcutaneous adipocytes from obese hyperinsulinemic women with polycystic ovary syndrome exhibit normal insulin sensitivity but reduced maximal insulin responsiveness
- 2005
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 153:6, s. 831-835
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polycystic ovary syndrome (PCOS) has a high prevalence in women and is often associated with insulin resistance and hence with aspects of the so-called metabolic syndrome.Methods: Ten women diagnosed with PCOS were consecutively included (aged 21-39 years, average 30.2 +/- 1.9 years: body mass index 28.4-42.5 kg/m(2), average 37.5 +/- 1.7 kg/m(2) (mean +/- S.E.)). Adipocytes were isolated from the subcutaneous fat and, after overnight incubation to recover from insulin resistance due to the surgical cell isolation procedures, they were analyzed for insulin sensitivity.Results: The patients with PCOS exhibited marked clinical hyperinsulinemia with 3.6-fold higher blood levels of C-peptide than a healthy lean control group (1.7 +/- 0.2 and 0.5 +/- 0.02 nmol/l respectively, P < 0.0001). The patients with PCOS also exhibited 2.4-fold higher concentrations of serum triacylglycerol (2.1 +/- 0.3 and 0.9 +/- 0.06 mmol/l respectively, P < 0.0001), but only slightly elevated blood pressure (118 +/- 12/76 +/- 6 and 113 +/- 7/72 +/- 6 mmHg respectively, P = 0.055/0.046). However, insulin sensitivity for stimulation of glucose transport in the isolated adipocytes was indistinguishable from a non-PCOS, non-diabetic control group, while the maximal insulin effect on glucose uptake was significantly lower (2.2 +/- 0.2- and 3.8 +/- 0.8-fold respectively, P = 0.02).Conclusions: Subcutaneous adipocytes from patients with PCOS do not display reduced insulin sensitivity. The findings show that the insulin resistance of PCOS is qualitatively different from that of type 2 diabetes.
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| 3. |
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| 4. |
- Tykesson, Emil, et al.
(författare)
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Recombinant dermatan sulfate is a potent activator of heparin cofactor II-dependent inhibition of thrombin
- 2019
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 29:6, s. 446-451
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Tidskriftsartikel (refereegranskat)abstract
- The glycosaminoglycan dermatan sulfate (DS) is a well-known activator of heparin cofactor II-dependent inactivation of thrombin. In contrast to heparin, dermatan sulfate has never been prepared recombinantly from material of non-animal origin. Here we report on the enzymatic synthesis of structurally well-defined DS with high anticoagulant activity. Using a microbial K4 polysaccharide and the recombinant enzymes DS-epimerase 1, dermatan 4-O-sulfotransferase 1, uronyl 2-O-sulfotransferase and N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase, several new glycostructures have been prepared, such as a homogenously sulfated IdoA-GalNAc-4S polymer and its 2-O-, 6-O- and 2,6-O-sulfated derivatives. Importantly, the recombinant highly 2,4-O-sulfated DS inhibits thrombin via heparin cofactor II, approximately 20 times better than heparin, enabling manipulation of vascular and extravascular coagulation. The potential of this method can be extended to preparation of specific structures that are of importance for binding and activation of cytokines, and control of inflammation and metastasis, involving extravasation and migration.
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| 5. |
- Westergren, Hanna, et al.
(författare)
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Glucose transport is equally sensitive to insulin stimulation, but basal and insulin-stimulated transport is higher, in human omental compared with subcutaneous adipocytes
- 2005
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495. ; 54:6, s. 781-785
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Tidskriftsartikel (refereegranskat)abstract
- Excess visceral fat has been found to correlate more closely with morbidity than subcutaneous fat. We found that isolated adipocytes from omental fat of nondiabetic women expressed significantly more of the insulin-regulated glucose transporter glucose transporter 4 protein and exhibited a higher basal and insulin-stimulated rate of glucose transport, at all concentrations of insulin, than subcutaneous adipocytes from the same individuals. In contrast, dose-response relationships for insulin stimulation of glucose transport demonstrated identical sensitivity to insulin in adipocytes from the 2 locations. The results demonstrate that there is no relative insulin resistance to stimulate glucose uptake in visceral compared with subcutaneous fat cells.
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| 6. |
- Zimmerman, Malin, et al.
(författare)
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Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1 diabetes
- 2017
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Ingår i: Journal of Clinical and Translational Endocrinology. - : Elsevier BV. - 2214-6237. ; 8, s. 15-21
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Tidskriftsartikel (refereegranskat)abstract
- Aim Diabetes mellitus type 1 (T1D) has numerous complications including autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their possible roles in effects of diabetes on the autonomic nervous system. Methods Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were analyzed. Results Autonomic nerve function deteriorated over time during the 20-year-period, but levels of HSP27, MIF, and PAI-1 were not associated with cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I-ratio. Conclusions Neither the neuroprotective substance HSP27 nor the inflammatory substances, MIF and PAI-1 were associated with measures of cardiovascular autonomic nerve function, but a deterioration of such function was observed in relation to increasing HbA1c in T1D during a 20-year follow-up period. Improved glucose control might be associated with protection against autonomic neuropathy in T1D.
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