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Homeobox gene expression and regulation in vascular myocytes

Gorski, David Henry
http://rave.ohiolink.edu/etdc/view?acc_num=case1057944521

Abstract Details

1994, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
This dissertation examines the potential roles of homeobox genes in growth regulation in vascular smooth muscle cells, a topic whose interest derives from its relevance to disease processes in which vascular myocyte proliferation is disordered, such as atherosclerosis. Abnormal proliferation of vascular smooth muscle cells is a critical component of the pathogenesis of both of these conditions, and very little is known about transcription factors which might play a role in regulating the entry of these cells into the cell cycle. To determine if homeobox transcription factors are involved in this process, a vascular cDNA library was screened with a degenerate oligonucleotide probe directed at the most conserved region of the homeodomain. Several homeobox cDNAs were isolated, including one that encodes Gax, a diverged homeobox gene that was subsequently found to be rapidly down-regulated when quiescent vascular smooth muscle cells were stimulated with serum growth factors. Further studies revealed another, previously described, homeobox gene which is responsive to serum growth factors, MHox/phox, whose transcript is rapidly up-regulated upon mitogen stimulation. Because of its unique pattern of expression, we tested recombinant Gax protein for its ability to inhibit the entry of vascular smooth muscle cells into S-phase. Gax inhibited the entry of quiescent vascular myocytes into S-phase by 40%. We compared this to MyoD and an anti-ras antibody, which inhibited vascular myocyte entry into S-phase by 36% and 65%, respectively. The growth inhibitory effect of microinjected Gax was dose-dependent and reversed by highly oncogenic ras mutant, Ras (Leu-61). Time course microinjection experiments suggested that Gax acts somewhere in late G1 to inhibit vascular myocyte proliferation. These experiments suggest that Gax is a negative regulator of growth in vascular myocytes, and that it is likely that Gax and other homeobox genes play a role in regulating the modulation of vascular myocytes from the contractile to the synthetic phenotype.
Kenneth Walsh (Advisor)
219 p.
Homeobox gene expression regulation vascular myocytes

Recommended Citations

Citations

  • Gorski, D. H. (1994). Homeobox gene expression and regulation in vascular myocytes [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1057944521

    APA Style (7th edition)

  • Gorski, David. Homeobox gene expression and regulation in vascular myocytes. 1994. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1057944521.

    MLA Style (8th edition)

  • Gorski, David. "Homeobox gene expression and regulation in vascular myocytes." Doctoral dissertation, Case Western Reserve University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=case1057944521

    Chicago Manual of Style (17th edition)

case1057944521
467
© 1994, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.