OASIS Modulates Hypoxia Pathway Activity to Regulate Bone Angiogenesis

Overview

Journal Sci Rep

Specialty Science

Date 2015 Nov 13

PMID 26558437

Citations 21

Authors

Min Cui

Soshi Kanemoto

Xiang Cui

Masayuki Kaneko

Rie Asada

Koji Matsuhisa

Keiji Tanimoto

Yuki Yoshimoto

Chisa Shukunami

Kazunori Imaizumi

Affiliations

Soon will be listed here.

Abstract

OASIS/CREB3L1, an endoplasmic reticulum (ER)-resident transcription factor, plays important roles in osteoblast differentiation. In this study, we identified new crosstalk between OASIS and the hypoxia signaling pathway, which regulates vascularization during bone development. RT-PCR and real-time PCR analyses revealed significant decreases in the expression levels of hypoxia-inducible factor-1α (HIF-1α) target genes such as vascular endothelial growth factor A (VEGFA) in OASIS-deficient (Oasis(-/-)) mouse embryonic fibroblasts. In coimmunoprecipitation experiments, the N-terminal fragment of OASIS (OASIS-N; activated form of OASIS) bound to HIF-1α through the bZIP domain. Luciferase assays showed that OASIS-N promoted the transcription activities of a reporter gene via a hypoxia-response element (HRE). Furthermore, the expression levels of an angiogenic factor Vegfa was decreased in Oasis(-/-) osteoblasts. Immunostaining and metatarsal angiogenesis assay showed retarded vascularization in bone tissue of Oasis(-/-) mice. These results suggest that OASIS affects the expression of HIF-1α target genes through the protein interaction with HIF-1α, and that OASIS-HIF-1α complexes may play essential roles in angiogenesis during bone development.

Citing Articles

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References

Omori Y, Imai J, Watanabe M, Komatsu T, Suzuki Y, Kataoka K . CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF family and functioning via the box-B element with a liver-specific expression. Nucleic Acids Res. 2001; 29(10):2154-62. PMC: 55463. DOI: 10.1093/nar/29.10.2154. View

Jiang H, Guo R, Powell-Coffman J . The Caenorhabditis elegans hif-1 gene encodes a bHLH-PAS protein that is required for adaptation to hypoxia. Proc Natl Acad Sci U S A. 2001; 98(14):7916-21. PMC: 35443. DOI: 10.1073/pnas.141234698. View

Tombran-Tink J, Barnstable C . Osteoblasts and osteoclasts express PEDF, VEGF-A isoforms, and VEGF receptors: possible mediators of angiogenesis and matrix remodeling in the bone. Biochem Biophys Res Commun. 2004; 316(2):573-9. DOI: 10.1016/j.bbrc.2004.02.076. View

Zelzer E, Mamluk R, Ferrara N, Johnson R, Schipani E, Olsen B . VEGFA is necessary for chondrocyte survival during bone development. Development. 2004; 131(9):2161-71. DOI: 10.1242/dev.01053. View

Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert S . The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest. 2007; 117(6):1616-26. PMC: 1878533. DOI: 10.1172/JCI31581. View

Ron D, Walter P . Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007; 8(7):519-29. DOI: 10.1038/nrm2199. View

Labrie C, Lessard J, Ben Aicha S, Savard M, Pelletier M, Fournier A . Androgen-regulated transcription factor AIbZIP in prostate cancer. J Steroid Biochem Mol Biol. 2007; 108(3-5):237-44. DOI: 10.1016/j.jsbmb.2007.09.008. View

Yamada S, Ohira M, Horie H, Ando K, Takayasu H, Suzuki Y . Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. Oncogene. 2004; 23(35):5901-11. DOI: 10.1038/sj.onc.1207782. View

Giaccia A, Simon M, Johnson R . The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease. Genes Dev. 2004; 18(18):2183-94. PMC: 517513. DOI: 10.1101/gad.1243304. View

10.

Hai T, Liu F, Coukos W, Green M . Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989; 3(12B):2083-90. DOI: 10.1101/gad.3.12b.2083. View

11.

ROLL D, Murphy B, Laderoute K, Sutherland R, Smith H . Oxygen regulated 80 kDa protein and glucose regulated 78kDa protein are identical. Mol Cell Biochem. 1991; 103(2):141-8. DOI: 10.1007/BF00227480. View

12.

Murphy B, Laderoute K, Short S, Sutherland R . The identification of heme oxygenase as a major hypoxic stress protein in Chinese hamster ovary cells. Br J Cancer. 1991; 64(1):69-73. PMC: 1977299. DOI: 10.1038/bjc.1991.241. View

13.

Cox J, Shamu C, Walter P . Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell. 1993; 73(6):1197-206. DOI: 10.1016/0092-8674(93)90648-a. View

14.

Gaut J, Hendershot L . The modification and assembly of proteins in the endoplasmic reticulum. Curr Opin Cell Biol. 1993; 5(4):589-95. DOI: 10.1016/0955-0674(93)90127-c. View

15.

Wang G, Jiang B, Rue E, Semenza G . Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995; 92(12):5510-4. PMC: 41725. DOI: 10.1073/pnas.92.12.5510. View

16.

Folkman J . Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995; 1(1):27-31. DOI: 10.1038/nm0195-27. View

17.

Jiang B, Rue E, Wang G, Roe R, Semenza G . Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem. 1996; 271(30):17771-8. DOI: 10.1074/jbc.271.30.17771. View

18.

Wei J, Hendershot L . Protein folding and assembly in the endoplasmic reticulum. EXS. 1996; 77:41-55. DOI: 10.1007/978-3-0348-9088-5_4. View

19.

Zhu C, Johansen F, Prywes R . Interaction of ATF6 and serum response factor. Mol Cell Biol. 1997; 17(9):4957-66. PMC: 232347. DOI: 10.1128/MCB.17.9.4957. View

20.

Lu R, Yang P, OHare P, Misra V . Luman, a new member of the CREB/ATF family, binds to herpes simplex virus VP16-associated host cellular factor. Mol Cell Biol. 1997; 17(9):5117-26. PMC: 232362. DOI: 10.1128/MCB.17.9.5117. View