title: Cellular reprogramming into a brown adipose tissue-like phenotype by co-expression of HB-EGF and ADAM 12S.
abstract: Abnormal adipogenesis leads to excessive fat accumulation and several health disorders. Mouse fibroblasts (MLC) transfected with ADAM 12S and HB-EGF promoted lipid accumulation. Addition of KBR-7785, an ADAM 12S inhibitor, to HB-EGF/ADAM 12S expressing cells suppressed adipogenesis. BrdU incorporation was attenuated and enhanced mitotracker staining was observed in HB-EGF/ADAM 12S cells. Quantitative real time RT-PCR resulted in elevated levels of expression of three brown adipose tissue (BAT) genes (PRDM16, PGC-1α, and UCP-1), while expression levels of the three white adipose tissue (WAT) genes (PPARγ, C/EBPα, and AKT-1) were unaltered in HB-EGF/ADAM 12S cells. Amino- or carboxy-terminal deletions of HB-EGF (HB-EGFΔN and HB-EGFΔC) co-expressed with ADAM 12S stimulated lipid accumulation. Human epidermoid carcinoma cells (A431) also exhibited lipid accumulation by HB-EGF/ADAM 12S co-expression. These studies suggest ADAM 12S and HB-EGF are involved in cellular plasticity resulting in the production of BAT-like cells and offers insight into novel therapeutic approaches for fighting obesity.
authors.affiliation: Department of Biology, Miami University , Oxford, OH , USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: M A
authors.initials: MA
authors.lastname: Darwal
authors.forename: E A
authors.initials: EA
authors.lastname: Cheng
authors.forename: S R
authors.initials: SR
authors.lastname: Taylor
authors.forename: E
authors.initials: E
authors.lastname: Duan
authors.forename: P A
authors.initials: PA
authors.lastname: Harding
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072199:ADAM12 Protein; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D002294:Carcinoma, Squamous Cell; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005347:Fibroblasts; D015870:Gene Expression; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D050356:Lipid Metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D010641:Phenotype; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D011994:Recombinant Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human