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Forkhead Box (forkhead + box)

Distribution by Scientific Domains
Medical Sciences80%

Terms modified by Forkhead Box

  • forkhead box p3
    		•

    Selected Abstracts

    Foxf1 +/, mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury

    HEPATOLOGY, Issue 1 2003
    Vladimir V. Kalinichenko
    Previous studies have shown that haploinsufficiency of the splanchnic and septum transversum mesoderm Forkhead Box (Fox) f1 transcriptional factor caused defects in lung and gallbladder development and that Foxf1 heterozygous (+/,) mice exhibited defective lung repair in response to injury. In this study, we show that Foxf1 is expressed in hepatic stellate cells in developing and adult liver, suggesting that a subset of stellate cells originates from septum transversum mesenchyme during mouse embryonic development. Because liver regeneration requires a transient differentiation of stellate cells into myofibroblasts, which secrete type I collagen into the extracellular matrix, we examined Foxf1 +/, liver repair following carbon tetrachloride injury, a known model for stellate cell activation. We found that regenerating Foxf1 +/, liver exhibited defective stellate cell activation following CCl4 liver injury, which was associated with diminished induction of type I collagen, ,,smooth muscle actin, and Notch-2 protein and resulted in severe hepatic apoptosis despite normal cellular proliferation rates. Furthermore, regenerating Foxf1 +/, livers exhibited decreased levels of interferon-inducible protein 10 (IP-10), delayed induction of monocyte chemoattractant protein 1 (MCP-1) levels, and aberrantly elevated expression of transforming growth factor ,1. In conclusion, Foxf1 +/, mice exhibited abnormal liver repair, diminished activation of hepatic stellate cells, and increased pericentral hepatic apoptosis following CCl4 injury. [source]

    Active FKHRL1 overcomes imatinib resistance in chronic myelogenous leukemia-derived cell lines via the production of tumor necrosis factor-related apoptosis-inducing ligand

    CANCER SCIENCE, Issue 12 2007
    Satoru Kikuchi
    FKHRL1 (also called FOXO3a) is a member of the Forkhead Box, class O (FOXO) subfamily of forkhead transcription factors and functions downstream of Bcr,Abl tyrosine kinase as a phosphorylated inactive form in chronic myelogenous leukemia (CML). The Bcr,Abl tyrosine kinase inhibitor imatinib induces cell cycle arrest and subsequent apoptosis via the conversion of FKHRL1 from the phosphorylated inactive form to the dephosphorylated active form in CML-derived cell lines. In the present study, we examined whether active FKHRL1 can overcome resistance to imatinib. To this end, we generated a 4-hydroxytamoxifen-inducible active FKHRL1 (FKHRL1-TM; a triple mutant of FKHRL1 in which all three Akt phosphorylation sites have been mutated),estrogen receptor fusion protein expression system in CML-derived imatinib-resistant cell lines. 4-Hydroxytamoxifen inhibited cell growth and cell cycle progression, and subsequently induced apoptosis, accompanied by upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Thus, active FKHRL1 antagonized deregulated proliferation and induced apoptosis in these cell lines. In addition, imatinib-resistant cells underwent apoptosis after transfection with full-length TRAIL cDNA. Collectively, our results suggest that active FKHRL1 can overcome imatinib resistance in CML cells, in part via TRAIL production. (Cancer Sci 2007; 98: 1949,1958) [source]

    Pertussis toxin activates adult and neonatal naive human CD4+ T,lymphocytes

    EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006
    Sandrine Tonon
    Abstract Pertussis toxin (PTX) is known to be mitogenic for T,lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA+CD4+ T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-, and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box,p3 (Foxp3) protein accumulation in naive CD4+ T cells. Addition of autologous dendritic cells was found to be required for the production of high levels of IFN-, by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-,B and NFAT transcription factors. Overall, responses of neonatal CD4+ T cells to PTX were similar to those of adult CD45RA+CD4+ naive T cells except for their blunted CD40 ligand up-regulation. We suggest that the adjuvant properties of PTX during primary cell-mediated immune responses involve a direct action on naive T,lymphocytes in addition to activation of antigen-presenting cells. [source]

    Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b

    HEPATOLOGY, Issue 6 2003
    Katherine Krupczak-Hollis
    The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and the members of which play essential roles in cellular proliferation, differentiation, and longevity. Reduced cellular proliferation during aging is associated with a progressive decline in both growth hormone (GH) secretion and Foxm1b expression. Liver regeneration studies with 12-month-old (old-aged) transgenic mice indicated that increased hepatocyte expression of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver. GH therapy in older people has been shown to cause an increase in cellular proliferation, but the transcription factors that mediated this stimulation in proliferation remain uncharacterized. In this study, we showed that human GH administration to old-aged Balb/c mice dramatically increased both expression of Foxm1b and regenerating hepatocyte proliferation. This increase in old-aged regenerating hepatocyte proliferation was associated with elevated protein expression of Cdc25A, Cdc25B, and cyclin B1, with reduced protein levels of cyclin-dependent kinase inhibitor p27Kip1 (p27). GH treatment also was found to stimulate hepatocyte proliferation and expression of Foxm1b protein without partial hepatectomy (PHx). Furthermore, GH treatment of young Foxm1b ,/, mice failed to restore regenerating hepatocyte DNA replication and mitosis caused by Foxm1b deficiency. These genetic studies provided strong evidence that the presence of Foxm1b is essential for GH to stimulate regenerating hepatocyte proliferation. In conclusion, our old-aged liver regeneration studies show that increased Foxm1b levels are essential for GH to stimulate hepatocyte proliferation, thus providing a mechanism for GH action in the elderly. [source]

    Transcriptional regulation of aquaporin 3 by insulin

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2007
    Shota Higuchi
    Abstract In the current study, we identified a regulatory factor for the transcription of aquaporin 3 (AQP3) whose expression is repressed by insulin. We constructed a luciferase reporter vector containing bp ,1382 to ,12 of the 5,-flanking region of the AQP3 gene for a reporter gene assay and observed that luciferase activity in transfectants with the plasmid decreased on treatment with insulin. Serial deletion constructs revealed two regions responsible for the insulin-mediated repression, one between bps ,1382 and ,780, and the other between bps ,404 and ,82. mRNA expression of forkhead box a2 (Foxa2), the binding site of which was located between bps ,1382 and ,780, was found to decrease on treatment with insulin. A mutant reporter plasmid with an altered Foxa2-binding site and siRNA for the Foxa2 sequence counteracted the insulin-mediated repression of AQP3 transcription. These results suggest that Foxa2 is one of the transcriptional regulators for AQP3 gene expression regulated by insulin. J. Cell. Biochem. 102: 1051,1058, 2007. © 2007 Wiley-Liss, Inc. [source]