Role of the Transcription Factor MAFA in the Maintenance of Pancreatic beta-Cells

Pancreatic beta-cells are specialized to properly regulate blood glucose. Maintenance of the mature beta-cell phenotype is critical for glucose metabolism, and beta-cell failure results in diabetes mellitus. Recent studies provide strong evidence that the mature phenotype of beta-cells is maintained by several transcription factors. These factors are also required for beta-cell differentiation from endocrine precursors or maturation from immature beta-cells during pancreatic development. Because the reduction or loss of these factors leads to beta-cell failure and diabetes, inducing the upregulation or inhibiting downregulation of these transcription factors would be beneficial for studies in both diabetes and stem cell biology. Here, we discuss one such factor, i.e., the transcription factor MAFA. MAFA is a basic leucine zipper family transcription factor that can activate the expression of insulin in beta-cells with PDX1 and NEUROD1. MAFA is indeed indispensable for the maintenance of not only insulin expression but also function of adult beta-cells. With loss of MAFA in type 2 diabetes, beta-cells cannot maintain their mature phenotype and are dedifferentiated. In this review, we first briefly summarize the functional roles of MAFA in beta-cells and then mainly focus on the molecular mechanism of cell fate conversion regulated by MAFA.