Department of Molecular Biology, School of Medicine, International University of Health and Welfare, Narita 286-8686, Chiba, Japan.
Division of Anatomy, Bio-Imaging and Neuro-Cell Science, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan.
Int J Mol Sci. 2022 Apr 19;23(9):4478. doi: 10.3390/ijms23094478.
Pancreatic β-cells are specialized to properly regulate blood glucose. Maintenance of the mature β-cell phenotype is critical for glucose metabolism, and β-cell failure results in diabetes mellitus. Recent studies provide strong evidence that the mature phenotype of β-cells is maintained by several transcription factors. These factors are also required for β-cell differentiation from endocrine precursors or maturation from immature β-cells during pancreatic development. Because the reduction or loss of these factors leads to β-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 β-cells with PDX1 and NEUROD1. MAFA is indeed indispensable for the maintenance of not only insulin expression but also function of adult β-cells. With loss of MAFA in type 2 diabetes, β-cells cannot maintain their mature phenotype and are dedifferentiated. In this review, we first briefly summarize the functional roles of MAFA in β-cells and then mainly focus on the molecular mechanism of cell fate conversion regulated by MAFA.
胰岛β细胞具有调节血糖的特性。成熟β细胞表型的维持对葡萄糖代谢至关重要，而β细胞衰竭则会导致糖尿病。最近的研究提供了强有力的证据表明，几种转录因子维持着成熟β细胞的表型。这些因子对于内分泌前体细胞向β细胞的分化或胰腺发育过程中不成熟β细胞的成熟也是必需的。由于这些因子的减少或丧失会导致β细胞衰竭和糖尿病，因此上调这些转录因子或抑制其下调对糖尿病和干细胞生物学的研究都是有益的。在这里，我们讨论了这样一个因子，即转录因子 MAFA。MAFA 是一种碱性亮氨酸拉链家族转录因子，可与 PDX1 和 NEUROD1 一起激活β细胞中胰岛素的表达。MAFA 对于维持不仅是胰岛素的表达，还有成年β细胞的功能是不可或缺的。在 2 型糖尿病中，MAFA 的缺失使β细胞无法维持其成熟表型，发生去分化。在这篇综述中，我们首先简要总结了 MAFA 在β细胞中的功能作用，然后主要关注 MAFA 调节的细胞命运转换的分子机制。
