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Mechanotransduction in Endothelial Cells:Cell Growth, Angiogenesis and Wound Healing

Liu, Jie
http://rave.ohiolink.edu/etdc/view?acc_num=osu1274392778

Abstract Details

2010, Doctor of Philosophy, Ohio State University, Dentistry.
Endothelial cells are mechano-sensitive cells and can perceive and respond to the biophysical changes in their microenvironment. However the molecular basis of the mechanisms by which endothelial cells perceive mechanical signals and relay them intracellularly to regulate gene expression remain unclear. It was our hypothesis that, signals generated by dynamic mechanical strain control human microvascular endothelial cell functions with high fidelity and spatial precision to regulate cell cycle progression and proliferation to promote angiogenesis in health and in disease. Our in vitro and in vivo investigations demonstrate that mechanoactivation of human endothelial cells results in (i) transcriptome wide upregulation of genes involved in angiogenesis and tissue repair, (ii) activation of signaling cascades initiated by vascular endothelial growth factor receptor-2 (VEGFR2) and integrin linked kinase, (iii) activation of Akt signaling cascade via phosphotidyl inositol-3 kinase (PI3K)-dependent Ser473-Akt phosphorylation and subsequent activation of signaling events which augment cell cycle progression and cell proliferation, (v) activation of ERK1/2 signaling cascade to promote angiogenesis (vi) suppression of IL-1β-induced proinflammatory gene transcription to support increased endothelial cell survival and cell proliferation, and (vii) persistence of pro-angiogenic effects of mechanical signals in the presence of pro-inflammatory cytokines. More importantly, the upregulation of angiogenesis by mechanical forces appears to play an important role in the increased induction of angiogenesis and more rapid wound resolution in vivo. The findings provide the molecular and biophysical basis by which mechanical forces, signaling molecules and transcription factors interplay to control cell growth and tissue organization. Furthermore, the findings provide the first evidence for the potential of mechanical signals in controlling tissue morphogenesis and open up new therapeutic options for wound healing and other angiogenesis dependent diseases.
Sudha Agarwal, PhD (Advisor)
Hiranmoy Das, PhD (Committee Member)
Sarandeep Huja, PhD (Committee Member)
Binnaz Leblebicioglu, PhD (Committee Member)
John Walters, MS (Committee Member)
130 p.
Cellular Biology
endothelial cell; angiogenesis, wound healing

Recommended Citations

Citations

  • Liu, J. (2010). Mechanotransduction in Endothelial Cells:Cell Growth, Angiogenesis and Wound Healing [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1274392778

    APA Style (7th edition)

  • Liu, Jie. Mechanotransduction in Endothelial Cells:Cell Growth, Angiogenesis and Wound Healing. 2010. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1274392778.

    MLA Style (8th edition)

  • Liu, Jie. "Mechanotransduction in Endothelial Cells:Cell Growth, Angiogenesis and Wound Healing." Doctoral dissertation, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1274392778

    Chicago Manual of Style (17th edition)

osu1274392778
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© 2010, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.