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This corrects the article DOI: 10.1038/onc.2017.277.
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The formation of a bipolar mitotic spindle is an essential process for the equal segregation of duplicated DNA into two daughter cells during mitosis. As a result of deregulated cellular signaling pathways, cancer cells often suffer a loss of genome integrity that might etiologically contribute to carcinogenesis. Merkel cell polyomavirus (MCV) small T (sT) oncoprotein induces centrosome overduplication, aneuploidy, chromosome breakage and the formation of micronuclei by targeting cellular ligases through a sT domain that also inhibits MCV large T oncoprotein turnover. These results provide important insight as to how centrosome number and chromosomal stability can be affected by the E3 ligase targeting capacity of viral oncoproteins such as MCV sT, which may contribute to Merkel cell carcinogenesis.
Assuntos
Antígenos Transformantes de Poliomavirus/metabolismo , Instabilidade Genômica , Poliomavírus das Células de Merkel/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Antígenos Transformantes de Poliomavirus/genética , Linhagem Celular , Transformação Celular Neoplásica/genética , Centrossomo/metabolismo , Centrossomo/virologia , Células HCT116 , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Células de Merkel/metabolismo , Células de Merkel/virologia , Poliomavírus das Células de Merkel/genética , Poliomavírus das Células de Merkel/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Células NIH 3T3RESUMO
Crescentic glomerulonephritis shows active and progressive glomerular changes with rapid deterioration in kidney function. A large dose of glucocorticoid (pulse therapy) is clinically used for the treatment, but its efficacy has not been fully estimated. In this study we assessed the therapeutic effect of a large dose of methyl-prednisolone (MP) on a rat model of crescentic glomerulonephritis that had been induced in WKY rats by an injection of anti-glomerular basement membrane antibody. The infiltration of CD8+ cells and monocytes was manifest by day 3, proteinuria appeared on days 4 and 5, and cellular crescents were diffusely formed by day 7. The gene expression of MCP-1, a chemokine for monocytes and T lymphocytes, was enhanced within 4 hours and peaked on day 3. Daily administration of MP (30 mg/kg/d) from day 3 through day 6 reduced the gene expression of MCP-1 and the numbers of glomerular leukocytes and largely prevented both crescent formation and proteinuria. When daily MP treatment started on day 7, the numbers of glomerular CD8+ cells and monocytes, crescents, and urinary protein were significantly reduced by day 11. In addition, continuing treatment with a small dose of MP (3 mg/kg/d) begun on day 11 completely prevented the increase in blood urea nitrogen and serum creatinine levels. These results indicate that treatment with a large dose of MP histologically and clinically ameliorates crescentic glomerulonephritis in a rat model, supporting the efficacy of pulse MP therapy for the treatment of the disease in human subjects.
Assuntos
Glomerulonefrite/tratamento farmacológico , Glucocorticoides/farmacologia , Metilprednisolona/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Northern Blotting , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Quimiocina CCL2/genética , Creatinina/sangue , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Humanos , Glomérulos Renais/patologia , Contagem de Leucócitos , Proteinúria/tratamento farmacológico , Proteinúria/imunologia , Proteinúria/patologia , Pulsoterapia , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos WKYRESUMO
Lymphotactin (LTN) is the sole member of C chemokine, the third subfamily of chemokines. LTN has been shown to be a chemoattractant specific for CD8+ cells and/or natural killer (NK) cells, and to be produced by CD8+ T cells, NK cells, and mast cells. However, there have been no reports describing its expression in clinical or experimental models of diseases so far. Since glomerular infiltration of CD8+ cells is prominent in an animal model of crescentic glomerulonephritis induced in WKY rats by an injection of anti-glomerular basement membrane antibody, we investigated the gene expression of LTN in this model. LTN mRNA was not detected in normal glomeruli but was detected at 0.5 h after the antibody injection, which detection preceded the infiltration of CD8+ cells. The expression of LTN mRNA peaked on day 3 and decreased thereafter. We next studied the expression of LTN mRNA in cultured glomerular and vascular cells, and found that glomerular mesangial and vascular endothelial cells could express LTN mRNA when stimulated with IL-1beta. These results indicate that the gene expression of LTN is enhanced in the animal model of glomerulonephritis and that intrinsic renal cells are the potential source of the gene expression of LTN in the kidney.
