Skip to main content
SpringerLink
Log in

Cloning of the 5′-flanking region of the murine bone morphogenetic protein-7 gene

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

BMP-7, a member of the bone morphogenetic protein subfamily of the TGFβ-superfamily is highly expressed in the murine kidney. BMP-7 is involved in fetal nephron development and mesenchymal to epithelial cell differentiation. Constitutive BMP-7 expression is found in tubular and glomerular epithelial cells of the adult kidney. BMP-7 may play a role in physiology and pathophysiology of the adult kidney since BMP-7 gene expression in acute renal ischemia is diminished and injection of recombinant BMP-7 into rats with ischemic acute renal failure preserves renal function. In order to investigate the transcriptional regulation of BMP-7, this study was undertaken to clone and characterize the promoter of the murine BMP-7 gene. A 1394 bp sequence of the 5′-flanking region of the BMP-7 gene was isolated and subcloned. No TATA and CAAT box consensus motifs could be identified as shown for promoters of other BMPs. Using in vitro transfection assays, the 5′-flanking region revealed moderate to strong basal promoter activity. PMA increased basal BMP-7 promoter activity. Thus BMP-7 gene transcription might involve at least in part a PKC-dependent pathway. The cloning of a 5′-flanking region of the BMP-7 gene should provide a useful tool for future studies on the transcriptional regulation of BMP-7 gene expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Massague J: The transforming growth factor-beta family. Annu Rev Cell Biol 6: 597–641, 1990

    Google Scholar 

  2. Ying SY: Inhibins, activins and follistatins. J Steroid Biochem 33: 705–713, 1989

    Google Scholar 

  3. Lyons KM, Jones CM, Hogan BL: The DVR gene family in embryonic development. Trends Genet 7: 408–412, 1991

    Google Scholar 

  4. Sporn MB, Roberts AB: Transforming growth factor-beta: Recent progress and new challenges. J Cell Biol 119: 1017–1021, 1992

    Google Scholar 

  5. Urist MR: Bone: Formation by autoinduction. Science 150: 893–899, 1965

    Google Scholar 

  6. Sampath TK, Reddi AH: Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. Proc Natl Acad Sci USA 78: 7599–7603, 1981

    Google Scholar 

  7. Urist MR, Huo YK, Brownell AG, Hohl WM, Buyske J, Lietze A, Tempst P, Hunkapiller M, DeLange RJ: Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography. Proc Natl Acad Sci USA 81: 371–375, 1984

    Google Scholar 

  8. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA: Novel regulators of bone formation: Molecular clones and activities. Science 242: 1528–1534, 1988

    Google Scholar 

  9. Vukicevic S, Helder MN, Luyten FP: Developing human lung and kidney are major sites for synthesis of bone morphogenetic protein-3 (osteogenin). J Histochem Cytochem 42: 869–875, 1994

    Google Scholar 

  10. Takahashi H, Ikeda T: Transcripts for two members of the transforming growth factor-beta superfamily BMP-3 and BMP-7 are expressed in developing rat embryos. Dev Dyn 207: 439–449, 1996

    Google Scholar 

  11. Suzuki A, Nishimatsu S, Murakami K, Ueno N: Differential expression of Xenopus BMPs in early embryos and tissues. Zoolog Sci 10: 175–178, 1993

    Google Scholar 

  12. Ozkaynak E, Schnegelsberg PN, Jin DF, Clifford GM, Warren FD, Drier EA, Oppermann H: Osteogenic protein-2. A new member of the transforming growth factor-beta superfamily expressed early in embryogenesis. J Biol Chem 267: 25220–25227, 1992

    Google Scholar 

  13. Lyons KM, Pelton RW, Hogan BL: Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A). Development 109: 833–844, 1990

    Google Scholar 

  14. Lyons KM, Pelton RW, Hogan BL: Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor-betalike genes coordinately regulate aspects of embryonic development. Genes Dev 3: 1657–1668, 1989

    Google Scholar 

  15. Knittel T, Fellmer P, Muller L, Ramadori G: Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and upregulated by transforming growth factor-beta 1. Exp Cell Res 232: 263–269, 1997

    Google Scholar 

  16. Jones CM, Lyons KM, Hogan BL: Involvement of bone morphogenetic protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111: 531–542, 1991

    Google Scholar 

  17. Helder MN, Ozkaynak E, Sampath KT, Luyten FP, Latin V, Oppermann H, Vukicevic S: Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in human and mouse development. J Histochem Cytochem 43: 1035–1044, 1995

    Google Scholar 

  18. Lyons KM, Hogan BL, Robertson EJ: Colocalization of BMP 7 and BMP 2 RNAs suggests that these factors cooperatively mediate tissue interactions during murine development. Mech Dev 50: 71–83, 1995

    Google Scholar 

  19. Ozkaynak E, Schnegelsberg PN, Oppermann H: Murine osteogenic protein (OP-1): High levels of mRNA in kidney. Biochem Biophys Res Commun 179: 116–123, 1991

    Google Scholar 

  20. Dudley AT, Lyons KM, Robertson EJ: A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 9: 2795–2807, 1995

    Google Scholar 

  21. Luo G, Hofmann C, Bronckers AL, Sohocki M, Bradley A, Karsenty G: BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 9: 2808–2820, 1995

    Google Scholar 

  22. Vukicevic S, Kopp JB, Luyten FP, Sampath TK: Induction of nephrogenic mesenchyme by osteogenic protein 1 (bone morphogenetic protein 7). Proc Natl Acad Sci USA 93: 9021–9026, 1996

    Google Scholar 

  23. Dudley AT, Godin RE, Robertson EJ: Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme. Genes Dev 13: 1601–1613, 1999

    Google Scholar 

  24. Godin RE, Takaesu NT, Robertson EJ, Dudley AT: Regulation of BMP7 expression during kidney development. Development 125: 3473–3482, 1998

    Google Scholar 

  25. Bhandari B, Beckwith KD, Miller RE: Cloning, nucleotide sequence, and potential regulatory elements of the glutamine synthetase gene from murine 3T3-L1 adipocytes. Proc Natl Acad Sci USA 85: 5789–5793, 1988

    Google Scholar 

  26. Sanger F, Nicklen S, Coulson AR: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977

    Google Scholar 

  27. Yee J, Kuncio GS, Bhandari B, Shihab FS, Neilson EG: Identification of promoter activity and differential expression of transcripts encoding the murine stromelysin-1 gene in renal cells. Kidney Int 52: 120–129, 1997

    Google Scholar 

  28. Herzlinger D, Koseki C, Mikawa T, al-Awqati Q: Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction. Development 114: 565–572, 1992

    Google Scholar 

  29. Simon M, Maresh JG, Harris SE, Hernandez JD, Arar M, Olson MS, Abboud HE: Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat kidney. Am J Physiol 276: F382–F389, 1999

    Google Scholar 

  30. Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV, Ignatieva EV, Ananko EA, Podkolodnaya OA, Kolpakov FA, Podkolodny NL, Kolchanov NA: Databases on transcriptional regulation: TRANSFAC, TRRD, and COMPEL. Nucleic Acids Res 26: 364–370, 1998

    Google Scholar 

  31. Sugiura T: Cloning and functional characterization of the 5′-flanking region of the human bone morphogenetic protein-2 gene. Biochem J 338: 433–440, 1999

    Google Scholar 

  32. Hino J, Takao M, Takeshita N, Konno Y, Nishizawa T, Matsuo H, Kangawa K: cDNA cloning and genomic structure of human bone morphogenetic protein-3B (BMP-3b). Biochem Biophys Res Commun 223: 304–310, 1996

    Google Scholar 

  33. Shore EM, Xu M, Shah PB, Janoff HB, Hahn GV, Deardorff MA, Sovinsky L, Spinner NB, Zasloff MA, Wozney JM, Kaplan FS: The human bone morphogenetic protein 4 (BMP-4) gene: Molecular structure and transcriptional regulation. Calcif Tissue Int 63: 221–229, 1998

    Google Scholar 

  34. Tamada H, Kitazawa R, Gohji K, Kamidono S, Maeda S, Kitazawa S: Molecular cloning and analysis of the 5′-flanking region of the human bone morphogenetic protein-6 (BMP-6). Biochim Biophys Acta 1395: 247–251, 1998

    Google Scholar 

  35. Sakaue M, Kitazawa S, Nishida K, Kitazawa R, Maeda S: Molecular cloning and characterization of human bone morphogenic protein (BMP)-5 gene promoter. Biochem Biophys Res Commun 221: 768–772, 1996

    Google Scholar 

  36. Kitten AM, Kreisberg JI, Olson MS: Expression of osteogenic protein-1 mRNA in cultured kidney cells. J Cell Physiol 181: 410–415, 1999

    Google Scholar 

  37. Pyke C, Kristensen P, Ostergaard PB, Oturai PS, Romer J: Proteoglycan expression in the normal rat kidney. Nephron 77: 461–470, 1997

    Google Scholar 

  38. Horowitz A, Simons M: Phosphorylation of the cytoplasmic tail of syndecan-4 regulates activation of protein kinase Calpha. J Biol Chem 273: 25548–25551, 1998

    Google Scholar 

  39. Oh ES, Woods A, Lim ST, Theibert AW, Couchman JR: Syndecan-4 proteoglycan cytoplasmic domain and phosphatidylinositol 4,5-bisphosphate coordinately regulate protein kinase C activity. J Biol Chem 273: 10624–10629, 1998

    Google Scholar 

  40. Chen RH, Ding WV, McCormick F: Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C. J Biol Chem 275: 17894–17899, 2000

    Google Scholar 

  41. Cadigan KM, Nusse R: Wnt signaling: A common theme in animal development. Genes Dev 11: 3286–3305, 1997

    Google Scholar 

  42. van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J, Ypma A, Hursh D, Jones T, Bejsovec A, Peifer M, Mortin M, Clevers H: Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88: 789–799, 1997

    Google Scholar 

Download references

Authors
  1. Matthias Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Denis Feliers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mazen Arar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Basant Bhandari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanna E. Abboud
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simon, M., Feliers, D., Arar, M. et al. Cloning of the 5′-flanking region of the murine bone morphogenetic protein-7 gene. Mol Cell Biochem 233, 31–37 (2002). https://doi.org/10.1023/A:1015546615027

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015546615027

Search

Navigation