2,4 -Dinitrophenol Trans-Differentiate NIH3T3 Cells into Insulin Producing β-Cells
2,4 -Dinitrophenol Trans-Differentiate NIH3T3 Cells into Insulin Producing β-Cells
Shumaila Usman1,2, Irfan Khan2, Kanwal Haneef3 and Asmat Salim2*
ABSTRACT
Diabetes is one of the most common diseases worldwide. Type I diabetes is characterized by the degeneration of β-cells. The present study is an attempt in the search of a suitable and efficient way to enhance the transdifferentiation ability of mature fibroblasts by using transgene free cellular approach in order to improve the cell-based therapeutics for diabetes. In the present study, we analyzed the effect of 2, 4 - Dinitrophenol (DNP) on the transdifferentiation of NIH3T3 cells into insulin producing β-cells (IPCs). DNP is a lipophilic weak acid that uncouple oxidative phosphorylation by decreasing ATP production. Cells treated with DNP were analyzed for the morphological changes and islet specific markers (MafA, Ngn3, Nkx 6.1, Pdx-1, insulin, glucagon, somatostatin and Sca-1) at gene and protein levels. In the presence of DNP, NIH3T3 cells appeared round, small and contracted while after reoxygenation they regained the normal fibroblast like spindle shaped morphology. The strategy to induce efficient transdifferentiation of NIH3T3 cells into IPCs has shown positive endocrine expression pattern, specifically β-cell specific transcription factors, demonstrating their successful regeneration. It is concluded that DNP has a potential to induce efficient transdifferentiation of NIH3T3 cells into insulin producing β-cells. The study could further be evaluated for their in vivo effect and serve as an improved and effective cellular therapeutic option for type 1 diabetes. It may offer the possibility of improved regeneration of damaged β-cells from mature cell type to functional insulin producing β-cells that could serve as a future therapeutic approach for diabetes.
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