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Sökning: LAR1:gu > Högskolan i Skövde > Lindahl Anders 1954

  • Resultat 1-4 av 4
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  • Holmgren, Gustav, et al. (författare)
  • MicroRNAs as potential biomarkers for doxorubicin-induced cardiotoxicity
  • 2016
  • Ingår i: Toxicology in Vitro. - 0887-2333. ; 34, s. 26-34
  • Tidskriftsartikel (refereegranskat)abstract
    • Anthracyclines, such as doxorubicin, are well-established, highly efficient anti-neoplastic drugs used for treatment of a variety of cancers, including solid tumors, leukemia, lymphomas, and breast cancer. The successful use of doxorubicin has, however, been hampered by severe cardiotoxic side-effects. In order to prevent or reverse negative side-effects of doxorubicin, it is important to find early biomarkers of heart injury and drug-induced cardiotoxicity. The high stability under extreme conditions, presence in various body fluids, and tissue-specificity, makes microRNAs very suitable as clinical biomarkers. The present study aimed towards evaluating the early and late effects of doxorubicin on the microRNA expression in cardiomyocytes derived from human pluripotent stem cells. We report on several microRNAs, including miR-34a, miR-34b, miR-187, miR-199a, miR-199b, miR-146a, miR-15b, miR-130a, miR-214, and miR-424, that are differentially expressed upon, and after, treatment with doxorubicin. Investigation of the biological relevance of the identified microRNAs revealed connections to cardiomyocyte function and cardiotoxicity, thus supporting the findings of these microRNAs as potential biomarkers for drug-induced cardiotoxicity.
  • Svala, E., et al. (författare)
  • Effects of interleukin-6 and interleukin-1 beta on expression of growth differentiation factor-5 and Wnt signaling pathway genes in equine chondrocytes
  • 2014
  • Ingår i: American Journal of Veterinary Research. - 0002-9645. ; 75:2, s. 132-140
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine the effects of interleukin (IL)-6 and IL-1β stimulation on expression of growth differentiation factor (GDF)-5 and Wnt signaling pathway genes in equine chondrocytes.SAMPLE: Macroscopically normal articular cartilage samples from 6 horses and osteochondral fragments (OCFs) from 3 horses.PROCEDURES: Chondrocyte pellets were prepared and cultured without stimulation or following stimulation with IL-6 or IL-1β for 1, 2, 12, and 48 hours; expression of GDF-5 was determined with a quantitative real-time PCR assay. Expression of genes in various signaling pathways was determined with microarrays for pellets stimulated for 1 and 2 hours. Immunohistochemical analysis was used to detect GDF-5, glycogen synthase kinase 3β (GSK-3β), and β-catenin proteins in macroscopically normal cartilage samples and OCFs.RESULTS: Chondrocytes stimulated with IL-6 had significantly higher GDF-5 expression within 2 hours versus unstimulated chondrocytes. Microarray analysis of Wnt signaling pathway genes indicated expression of GSK-3β and coiled-coil domain containing 88C increased after 1 hour and expression of β-catenin decreased after 2 hours of IL-6 stimulation. Results of immunohistochemical detection of proteins were similar to microarray analysis results. Chondrocytes in macroscopically normal articular cartilage and OCFs had immunostaining for GDF-5.CONCLUSION AND CLINICAL RELEVANCE: Results indicated IL-6 stimulation decreased chondrocyte expression of the canonical Wnt signaling pathway transactivator β-catenin, induced expression of inhibitors of the Wnt pathway, and increased expression of GDF-5. This suggested IL-6 may inhibit the Wnt signaling pathway with subsequent upregulation of GDF-5 expression. Anabolic extracellular matrix metabolism in OCFs may be attributable to GDF-5 expression. This information could be useful for development of cartilage repair methods.
  • Synnergren, Jane, et al. (författare)
  • Differentiating human embryonic stem cells express a unique housekeeping gene signature.
  • 2007
  • Ingår i: Stem cells (Dayton, Ohio). - 1066-5099. ; 25:2, s. 473-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Housekeeping genes (HKGs) are involved in basic functions needed for the sustenance of the cell and are assumed to be constitutively expressed at a constant level. Based on these features, HKGs are frequently used for normalization of gene expression data. In the present study, we used the CodeLink Gene Expression Bioarray system to interrogate changes in gene expression occurring during differentiation of human ESCs (hESCs). Notably, in the three hESC lines used for the study, we observed that the RNA levels of 56 frequently used HKGs varied to a degree that rendered them inappropriate as reference genes. Therefore, we defined a novel set of HKGs specifically for hESCs. Here we present a comprehensive list of 292 genes that are stably expressed (coefficient of variation <20%) in differentiating hESCs. These genes were further grouped into high-, medium-, and low-expressed genes. The expression patterns of these novel HKGs show very little overlap with results obtained from somatic cells and tissues. We further explored the stability of this novel set of HKGs in independent, publicly available gene expression data from hESCs and observed substantial similarities with our results. Gene expression was confirmed by real-time quantitative polymerase chain reaction analysis. Taken together, these results suggest that differentiating hESCs have a unique HKG signature and underscore the necessity to validate the expression profiles of putative HKGs. In addition, this novel set of HKGs can preferentially be used as controls in gene expression analyses of differentiating hESCs.
  • Synnergren, Jane, et al. (författare)
  • Transcriptional profiling of human embryonic stem cells differentiating to definitive and primitive endoderm and further toward the hepatic lineage.
  • 2010
  • Ingår i: Stem cells and development. - 1557-8534. ; 19:7, s. 961
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stem cells (hESC) can differentiate into a variety of specialized cell types, and they constitute a useful model system to study embryonic development in vitro. In order to fully utilize the potential of these cells, the mechanisms that regulate the developmental processes of specific lineage differentiation need to be better defined. The aim of this study was to explore the molecular program involved in the differentiation of hESC towards definitive endoderm (DE) and further into the hepatic lineage, and to compare that to primitive endoderm (PrE) differentiation. To that end, we applied two protocols, a specific DE differentiation protocol and an intrinsic differentiation protocol that mainly mediates PrE formation. We collected hESC, hESC-derived DE, DE-derived hepatocyte-progenitors (DE-Prog), DE-derived hepatocyte-like cells (DE-Hep), and the corresponding PrE-derivatives. The samples were analyzed using microarrays, and we identified sets of genes which were exclusively up-regulated in DE-derivatives (compared to PrE-derivatives) at discrete developmental stages. We also investigated known protein interactions among the set of up-regulated genes in DE-Hep. The results demonstrate important differences between DE- and PrE-differentiation on the transcriptional level. In particular, our results identify a unique molecular program, exclusively activated during development of DE and the subsequent differentiation of DE towards the hepatic lineage. We identified key-genes and pathways of potential importance for future efforts to improve hepatic differentiation from hESC. These results reveal new opportunities for rational design of specific interventions with the purpose of generating enriched populations of DE derivatives, including functional hepatocytes.
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