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Sean_Taylor_Dissertation_final.pdf (3.17 MB)

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Co-expression of HB-EGF and ADAM 12S displays a brown adipose phenotype in mouse and human cell lines.

Taylor, Sean R
http://orcid.org/0000-0001-8888-0097
http://rave.ohiolink.edu/etdc/view?acc_num=miami1524347780576749

Abstract Details

2018, Doctor of Philosophy, Miami University, Cell, Molecular and Structural Biology (CMSB).
Heparin-bind epidermal growth factor-like growth factor (HB-EGF) and a disintegrin and metalloproteinase 12 (ADAM 12) are involved in cell cycle progression and have been implicated in various cancers. Recently, our lab demonstrated that when HB-EGF and a short secreted form of ADAM 12, ADAM 12S, are co-expressed in fibroblastic cells, adipogenesis results. To further support these findings HB-EGF and ADAM 12S adenovirus was constructed, cells were infected, and lipid accumulation was replicated. Both stable transfected and adenoviral co-infected cells exhibited increased expression of PPARgamma Coactivator 1 alpha (PGC-1a), Fibroblast growth factor (FGF)-2, Kruppel-like factor (KLF)3, KLF4, and decreased expression of CCAAT/enhancer-binding protein alpha (C/EBP-a), Lamin A/C (LMNA), glucose transporter (GLUT)4, and Schmidt-Ruppin A-2 viral oncogene homolog (SRC) in human epidermoid carcinoma cells. Additionally, an analog of HB-EGF lacking functional cytoplasmic and amino (N)-terminal ligands results in lipid accumulation but does not demonstrate significant up-regulation of brown adipocyte marker genes. Interestingly human primary preadipocytes natively express HB-EGF and when infected with primary ADAM 12S adenovirus several small lipid droplets form (multilocular) and up-regulation of PGC-1a and down-regulation of PR domain containing (PRDM)16 are demonstrated. Furthermore HB-EGF/ADAM 12S co-expressing cells exhibit increased metabolic function similar to brown adipose tissue as demonstrated by oxygen consumption and extracellular acidification rates. Together this evidence suggests that HB-EGF and ADAM 12S co-expression results in a brown adipose tissue-like phenotype and the increased metabolic abilities of these cells may be a valuable therapeutic tool to combat metabolic diseases such as obesity and type II diabetes.
Paul Harding, Dr. (Advisor)
Paul Schaeffer, Dr. (Committee Chair)
Haifei Shi, Dr. (Committee Member)
Dawn Blitz, Dr. (Committee Member)
Danielson Neil, Dr. (Committee Member)
121 p.
Biology; Cellular Biology; Molecular Biology; Zoology
brown adipose tissue; obesity; cellular reprogramming; transdifferentiation; HB-EGF; ADAM 12S; metabolism

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Citations

  • Taylor, S. R. (2018). Co-expression of HB-EGF and ADAM 12S displays a brown adipose phenotype in mouse and human cell lines. [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1524347780576749

    APA Style (7th edition)

  • Taylor, Sean. Co-expression of HB-EGF and ADAM 12S displays a brown adipose phenotype in mouse and human cell lines. 2018. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1524347780576749.

    MLA Style (8th edition)

  • Taylor, Sean. "Co-expression of HB-EGF and ADAM 12S displays a brown adipose phenotype in mouse and human cell lines." Doctoral dissertation, Miami University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=miami1524347780576749

    Chicago Manual of Style (17th edition)

miami1524347780576749
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© 2018, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.