Cellular transdifferentiation into brown adipose-like cells by adenoviral-directed expression or stable transfection of HB-EGF and ADAM 12S

Adenoviral vectors directing the expression of HB-EGF and ADAM 12S were used to better understand the gene expression profile of cellular reprogramming into BAT-like cells compared to HB-EGF and ADAM 12S transfection. Human epidermoid carcinoma cells (A431) were co-infected with HB-EGF and ADAM 12S adenoviruses, monitored for fluorescence and lipid accumulation for 1-3 weeks. Cells were stained with Oil Red O and total RNA was harvested and analyzed with a human adipogenic RT Profiler Array. Additionally, the gene expression profile of RNA from A431 control cells and A431 cells stably transfected with HB-EGF and ADAM 12S were analyzed and compared to the gene expression patterns of adenoviral HB-EGF and ADAM 12S infected cells. Adenoviral HB-EGF ADAM 12S coinfected A431 RNA exhibited significant up-regulation of PGC-1α, Klf3, Klf4 and FGF-2 mRNA and downregulation of C/EBPα, LMNA, GLUT4 and SRC mRNA. RNA derived from HB-EGF and ADAM 12S co-transfected A431 cells exhibited similar gene expression profiles with the human adipogenic array. Adenovirus HB-EGF and ADAM 12S coinfected cells transdifferentiate human A431 cells into a BAT-like phenotype and recapitulate findings with HB-EGF and ADAM 12S transfected cells. The findings presented in this study identify genes important in BAT-like cellular reprogramming and may have therapeutic implications to obesity and type 2 diabetes.