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Co-expression of HB-EGF and ADAM 12S Displays a Brown Adipose Phenotype in Mouse and Human Cell Lines
Başlık:
Co-expression of HB-EGF and ADAM 12S Displays a Brown Adipose Phenotype in Mouse and Human Cell Lines
Yazar:
Taylor, Sean R., author.
ISBN:
9780438092792
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (123 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Paul Harding Committee members: Dawn Blitz; Danielson Neil; Paul Schaeffer; Haifei Shi.
Özet:
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-1alpha), Fibroblast growth factor (FGF)-2, Kruppel-like factor (KLF)3, KLF4, and decreased expression of CCAAT/enhancer-binding protein alpha (C/EBP-alpha), 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-1alpha 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.
Notlar:
School code: 0126
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(687054.1) | 687054-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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