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FoxO4 is the main forkhead transcriptional factor localized in the gastrointestinal tracts of pigs

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Abstract

Forkhead box (Fox) proteins play critical roles in the regulation of differentiation, proliferation, immunity and aging of cells. Most studies on Fox proteins are limited to cultured cells and rodent. The aim of the current study is to detect by immunohistrochemistry whether FoxO1, FoxO3a and FoxO4 proteins are localized in the stomach and intestine of the pig. The results showed that FoxO4 exists in the mucosa in all parts of the stomach and intestine; FoxO3a exists mainly in the lamina propria and muscularis of some parts. However, FoxO1 is not detectable in all parts of the stomach and intestine. Collectively, the results of the present study indicate that there exists a distinct expression pattern of Fox proteins, and that FoxO4 is a primary forkhead transcriptional factor localized in the gastrointestinal tracts of the pig.

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References

  • Accili, D., Arden, K.C., 2004. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 117(4):421–426. [doi:10.1016/S0092-8674(04)00452-0]

    Article  PubMed  CAS  Google Scholar 

  • Arden, K.C., Biggs, W.H., 2002. Regulation of the FoxO family of transcription factors by phosphatidylinositol-3 kinase-activated signaling. Arch. Biochem. Biophys., 403(2):292–298. [doi:10.1016/S0003-9861(02)00207-2]

    Article  PubMed  CAS  Google Scholar 

  • Barthélémy, C., Henderson, C.E., Pettmann, B., 2004. FoxO3a induces motoneuron death through the Fas pathway in cooperation with JNK. BMC Neurosci., 5(1):48. [doi:10.1186/1471-2202-5-48]

    Article  PubMed  CAS  Google Scholar 

  • Burgering, B.M., Kops, G.J., 2002. Cell cycle and death control: long live forkheads. Trends Biochem. Sci., 27(7):352–360. [doi:10.1016/S0968-0004(02)02113-8]

    Article  PubMed  CAS  Google Scholar 

  • Fernandez de Mattos, S., Essafi, A., Soeiro, I., Pietersen, A.M., Birkenkamp, K.U., Edwards, C.S., Martino, A., Nelson, B.H., Francis, J.M., Jones, M.C., et al., 2004. FoxO3a and BCR-ABL regulate cyclin D2 transcription through a STAT5/BCL6-dependent mechanism. Mol. Cell Biol., 24(22):10058–10071. [doi:10.1128/MCB.24.22.10058-10071.2004]

    Article  PubMed  CAS  Google Scholar 

  • Finnberg, N., El-Deiry, W.S., 2004. Activating FOXO3a, NF-kappaB and p53 by targeting IKKs: an effective multi-faceted targeting of the tumor-cell phenotype? Cancer Biol. Ther., 3(7):614–616.

    Article  PubMed  CAS  Google Scholar 

  • Fukuoka, M., Daitoku, H., Hatta, M., Matsuzaki, H., Umemura, S., Fukamizu, A., 2003. Negative regulation of forkhead transcription factor AFX (FoxO4) by CBP-induced acetylation. Int. J. Mol. Med., 12(4):503–508.

    PubMed  CAS  Google Scholar 

  • Graff, P., Amellem, O., Seim, J., Stokke, T., Pettersen, E.O., 2005. The role of p27 in controlling the oxygen-dependent checkpoint of mammalian cells in late G1. Anticancer Res., 25(3B):2259–2267.

    PubMed  CAS  Google Scholar 

  • Hoekman, M.F., Jacobs, F.M., Smidt, M.P., Burbach, J.P., 2006. Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain. Gene Expr. Patterns, 6(2):134–140. [doi:10.1016/j.modgep.2005.07.003]

    Article  PubMed  CAS  Google Scholar 

  • Hosaka, T., Biggs, W.H.3rd, Tieu, D., 2004. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc. Natl. Acad. Sci. USA, 101(9):2975–2980. [doi:10.1073/pnas.0400093101]

    Article  PubMed  CAS  Google Scholar 

  • Hu, M.C., Lee, D.F., Xia, W., Golfman, L.S., Ou-Yang, F., Yang, J.Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al., 2004. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell, 117(2):225–237. [doi:10.1016/S0092-8674(04)00302-2]

    Article  PubMed  CAS  Google Scholar 

  • Jacobs, F.M., van der Heide, L.P., Wijchers, P.J., Burbach, J.P., Hoekman, M.F., Smidt, M.P., 2003. FoxO6, a novel member of the FoxO class of transcription factors with distinct shuttling dynamics. J. Biol. Chem., 278(38):35959–35967. [doi:10.1074/jbc.M302804200]

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi, Y., Furukawa-Hibi, Y., Chen, C., Horio, Y., Isobe, K., Ikeda, K., Motoyema, N., 2005. SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. Int. J. Mol. Med., 16(2):237–243.

    PubMed  CAS  Google Scholar 

  • Li, X., Jiang, Y., Wang, Z., Liu, G., Hutz, R.J., Liu, W., Shi, F., 2005a. Regulation of FoxO1 transcription factor by nitric oxide and cyclic GMP in cultured rat granulosa cells. Zool. Sci., 22(12):1339–1346. [doi:10.2108/zsj.22.1339]

    Article  PubMed  CAS  Google Scholar 

  • Li, X., Xie, Z., Shi, F., 2005b. Involvement of forkhead box proteins in apoptosis and oncogenesis. Prog. Biochem. Biophs., 32(7):600–606.

    CAS  Google Scholar 

  • Li, X., Xie, Z., Shi, F., 2006. FOXO in the regulation of differentiation, proliferation, immunity and aging of cells. Chin. J. Clin. Rehabil., 10(9):158–162.

    CAS  Google Scholar 

  • Liu, Y., Lehmann, M., 2006. FOXO-independent suppression of programmed cell death by the PI3K/Akt signaling pathway in Drosophila. Dev. Genes Evol., 216(9):531–535. [doi:10.1007/s00427-006-0063-x]

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Gac, L., Marques, M., Garcia, Z., Campanero, M.R., Carrera, A.C., 2004. Control of cyclin G2 mRNA expression by forkhead transcription factors: novel mechanism for cell cycle control by phosphoinositide 3-kinase and forkhead. Mol. Cell. Biol., 24(5):2181–2189. [doi:10.1128/MCB.24.5.2181-2189.2004]

    Article  PubMed  CAS  Google Scholar 

  • Michl, P., Downward, J., 2005. PI3K/AKT signaling in gastrointestinal cancers. Z. Gastroenterol., 43(10):1133–1139. [doi:10.1055/s-2005-858638]

    Article  PubMed  CAS  Google Scholar 

  • Seoane, J., Le, H.V., Shen, L., Anderson, S.A., Massague, J., 2004. Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell, 117(2):211–223. [doi:10.1016/S0092-8674(04)00298-3]

    Article  PubMed  CAS  Google Scholar 

  • Shi, F., LaPolt, P.S., 2003. Relationship between FoxO1 protein levels and follicular development, atresia, and luteinization in the rat ovary. J. Endocrinol., 179(2):195–203. [doi:10.1677/joe.0.1790195]

    Article  PubMed  CAS  Google Scholar 

  • Skurk, C., Izumiya, Y., Maatz, H., Razeghi, P., Shiojima, I., Sandri, M., Sato, K., Zeng, L., Schiekofer, S., Pimentel, D., et al., 2005. The FoxO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling. J. Biol. Chem., 280(21):20814–20823. [doi:10.1074/jbc.M500528200]

    Article  PubMed  CAS  Google Scholar 

  • Stahl, M., Dijkers, P.F., Kops, G.J., Lens, S.M., Coffer, P.J., Burgering, B.M., Medema, R.H., 2002. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J. Immunol. (Baltimore, Md.: 1950), 168(10):5024–5031.

    CAS  Google Scholar 

  • Wang, T., Huo, Y.J., Shi, F., Xu, R.J., Hutz, R.J., 2005. Effects of intrauterine growth retardation on development of the gastrointestinal tract in neonatal pigs. Biol. Neonate, 88(1):66–72. [doi:10.1159/000084645]

    Article  PubMed  Google Scholar 

  • Weinkove, D., Halstead, J.R., Gems, D., Divecha, N., 2006. Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FoxO to the cytoplasm. BMC Biol., 4(1):1. [doi:10.1186/1741-7007-4-1]

    Article  PubMed  CAS  Google Scholar 

  • Yamamura, Y., Lee, W.L., Inoue, K., Ida, H., Ito, Y., 2006. RUNX3 cooperates with FOXO3a to induce apoptosis in gastric cancer cells. J. Biol. Chem., 281(8):5267–5276. [doi:10.1074/jbc.M512151200]

    Article  PubMed  CAS  Google Scholar 

  • Yang, H., Zhao, R., Yang, H.Y., Lee, M.H., 2005. Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 stability, and suppresses HER2-mediated tumorigenicity. Oncogene, 24(11):1924–1935. [doi:10.1038/sj.onc.1208352]

    Article  PubMed  CAS  Google Scholar 

  • Zhang, D.W., Li, X.Y., Chen, L.T., 2001. Animal models and pathological changes in gastroesophageal reflux. Chin. J. Pediatr. Surg., 22(2):112–114.

    Google Scholar 

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Correspondence to Shi Fang-xiong.

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Project supported by the National Basic Research Program (973) of China (No. 2004CB117500) and the National Natural Science Foundation of China (Nos. 30571335 and 330471253)

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Zhou, Zq., Wang, T., Pan, Lm. et al. FoxO4 is the main forkhead transcriptional factor localized in the gastrointestinal tracts of pigs. J. Zhejiang Univ. - Sci. B 8, 39–44 (2007). https://doi.org/10.1631/jzus.2007.B0039

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  • DOI: https://doi.org/10.1631/jzus.2007.B0039

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