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BIOLOGICAL SIGNIFICANCE OF HEPARIN-BINDING GROWTH FACTORS HB-EGF AND CTGF

Zhou, Zhenqing
http://rave.ohiolink.edu/etdc/view?acc_num=miami1258498601

Abstract Details

2009, Doctor of Philosophy, Miami University, Zoology.
Typically growth factors act as signaling molecules between cells, playing an important role in cellular proliferation and differentiation. A variety of growth factors are able to bind heparin, and this binding activity is important in sequestering growth factors in the extracellular matrix (ECM), serving to prevent growth factor degradation and enhancing binding to cell surface receptors. Two examples are heparin-binding epidermal growth factor-like growth factor (HB-EGF) and connective tissue growth factor (CTGF). Both function rather broadly to induce wound healing and modulate function in a wide range of cell types. HB-EGF was identified as an adipocytokine whose expression correlates with obesity, a condition characterized by excessive adipose tissue which could cause serious health problems, including diabetes, hypertension, cancer and cardiovascular diseases. Soluble HB-EGF and its signal transduction are specific important molecules in regulation of tissue development and growth. A disintegrin and metalloprotease 12 (ADAM 12) proteolytically cleaves the membrane-anchored HB-EGF to release soluble HB-EGF. The interactions between HB-EGF and ADAM 12 trigger intracellular signal-transduction cascades that result in adipocyte differentiation. The effects of HB-EGF and ADAM 12 on adipogenesis in mouse fibroblasts and human cancer cells are reported here. The heparin binding growth factor CTGF promotes fibroblast adhesion, migration, proliferation, and extracellular matrix formation, and its overexpression plays a major role in pathways that lead to fibrosis, a condition marked by increased fibrous tissue that harmfully influences normal organ functions. Transforming growth factor (TGF) -β is well known to be a critical factor that induces CTGF and type I collagen gene expression and leads to fibrosis. However, CTGF can cause fibrosis through TGF-β independent pathways. The biological role of CTGF in the development of testicular fibrosis using a transgenic mouse model is described here. These studies provide new insights into understanding the biological significance of heparin-binding growth factors.
Paul Harding (Advisor)
Paul James (Committee Member)
Jack Vaughn (Committee Member)
Katia Del Rio-Tsonis (Committee Chair)
Michael Crowder (Committee Member)
183 p.
Biomedical Research
HB-EGF; CTGF; brown adipose tissue; white adipose tissue; testicular fibrosis; PRDM16; type I collagen; obesity; diabetes; transdifferentiation

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Citations

  • Zhou, Z. (2009). BIOLOGICAL SIGNIFICANCE OF HEPARIN-BINDING GROWTH FACTORS HB-EGF AND CTGF [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1258498601

    APA Style (7th edition)

  • Zhou, Zhenqing. BIOLOGICAL SIGNIFICANCE OF HEPARIN-BINDING GROWTH FACTORS HB-EGF AND CTGF. 2009. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1258498601.

    MLA Style (8th edition)

  • Zhou, Zhenqing. "BIOLOGICAL SIGNIFICANCE OF HEPARIN-BINDING GROWTH FACTORS HB-EGF AND CTGF." Doctoral dissertation, Miami University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=miami1258498601

    Chicago Manual of Style (17th edition)

miami1258498601
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© 2009, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.