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  • EXPRESSION  (3)
  • 1
    Keywords: EXPRESSION ; GROWTH ; IN-VITRO ; INHIBITOR ; proliferation ; CELL ; CELL-PROLIFERATION ; Germany ; human ; IN-VIVO ; VITRO ; VIVO ; microarray ; PROTEIN ; PROTEINS ; RNA ; DRUG ; SURGERY ; PATIENT ; REDUCTION ; TRANSPLANTATION ; RAT ; CONTRAST ; mechanisms ; SKIN ; fibroblasts ; ACID ; PCR ; NUCLEOTIDES ; EXTRACELLULAR-MATRIX ; ADHESION ; MIGRATION ; cytoskeleton ; POLYMERASE-CHAIN-REACTION ; SMOOTH-MUSCLE ; COMPLICATIONS ; BIOPSY ; CHAIN ; fibroblast ; DEHYDROGENASE ; RECIPIENTS ; HUMAN FIBROBLASTS ; cell adhesion ; mycophenolic acid ; TECHNOLOGY ; B-LYMPHOCYTES ; ENGLAND ; ACTIN ; DYSFUNCTION ; synthesis ; NUCLEOTIDE ; CYCLOSPORINE ; MOFETIL ; KIDNEY-TRANSPLANT
    Abstract: Mycophenolic acid (MPA) is a potent inhibitor of the inosine monophosphate dehydrogenase and used as an immunosuppressive drug in transplantation. MPA inhibits proliferation of T- and B-lymphocytes by guanosine depletion. Since fibroblasts rely on the de novo synthesis of guanosine nucleotides, it is assumed that MPA interacts with fibroblasts causing an increased frequency of wound healing problems. We show a downregulation of the cytoskeletal proteins vinculin, actin and tubulin in fibroblasts exposed to pharmacological doses of MPA using microarray technology, real-time polymerase chain reaction (PCR) and Western blot. This reduction in RNA and protein content is accompanied by a substantial rearrangement of the cytoskeleton in MPA-treated fibroblasts as documented by immunofluorescence. The dysfunctional fibroblast growth was validated by scratch test documenting impaired migrational capacity. In contrast, cell adhesion was increased in MPA-treated fibroblasts. The results of the cultured human fibroblasts were applied to skin biopsies of renal transplant recipients. Skin biopsies of patients treated with MPA expressed less vinculin, actin and tubulin as compared to control biopsies that could explain potential wound healing problems posttransplantation. The perspective of MPA-induced cytoskeletal dysfunction may go beyond wound healing disturbances and may have beneficial effects on (renal) allografts with respect to scarring
    Type of Publication: Journal article published
    PubMed ID: 18786225
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  • 2
    Keywords: CANCER ; EXPRESSION ; TUMORS ; p53 ; HPV ; SQUAMOUS-CELL CARCINOMA ; INDIVIDUALS ; p16(INK4A) ; TRANSPLANT RECIPIENTS ; STAPHYLOCOCCUS-AUREUS
    Abstract: BACKGROUND: High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention. METHODS: High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16(INK4a), a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically. RESULTS: The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16(INK4a) expression in most SCC (P〈0.001) and basal cell cancers (P = 0.02), while almost all SCC in situ were p16(INK4a) positive irrespective of HR-HPV presence (P = 0.66). Diffuse p16(INK4a) expression was associated with lack of pRB expression (P = 0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence. CONCLUSION: High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16(INK4a) expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions
    Type of Publication: Journal article published
    PubMed ID: 21427726
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  • 3
    Keywords: EXPRESSION ; CUTTING EDGE ; MECHANISM ; ALPHA ; MEMBRANE ; microglia ; GAMMA ; FUNCTIONAL GAP-JUNCTIONS ; NANOTUBES
    Abstract: Transfer of cellular material via tunneling nanotubes (TNT) was recently discovered as a novel mechanism for intercellular communication. The role of intercellular exchange in communication of renal epithelium is not known. Here we report extensive spontaneous intercellular exchange of cargo vesicles and organelles between primary human proximal tubular epithelial cells (RPTEC). Cells were labeled with two different quantum dot nanocrystals (Qtracker 605 or 525) and intercellular exchange was quantified by high-throughput fluorescence imaging and FACS analysis. In co-culture, a substantial fraction of cells (67.5%) contained both dyes indicating high levels of spontaneous intercellular exchange in RPTEC. The double positive cells could be divided into three categories based on the preponderance of 605 Qtracker (46.30%), 525 Qtracker (48.3%) and approximately equal content of both Qtrackers (4.57%). The transfer of mitochondria between RPTECs was also detected using an organelle specific dye. Inhibition of TNT genesis by actin polymerization inhibitor (Latrunculin B) markedly reduced intercellular exchange (〉60%) suggesting that intercellular exchange in RPTEC was in part mediated via TNT-like structures. In contrast, induction of cellular stress by Zeocin treatment increased tube-genesis in RPTEC. Our data i
    Type of Publication: Journal article published
    PubMed ID: 21738629
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