Abstract
Pax4 and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A) are two transcription factors crucial for normal functions of islet beta cells in the mouse. Intriguingly, recent studies indicate the existence of notable difference between human and rodent islet in terms of gene expression and functions. To better understand the biological role of human PAX4 and MAFA, we investigated their expression in normal and diseased human islets, using validated antibodies. PAX4 was detected in 43.0±5.0% and 39.1±4.0% of normal human alpha and beta cells respectively. We found that MAFA, detected in 88.3±6.3% insulin+cells as in the mouse, turned out to be also expressed in 61.2±6.4% of human glucagons+ cells with less intensity than in insulin+ cells, whereas MAFB expression was found not only in the majority of glucagon+ cells (67.2±7.6%), but also in 53.6±10.5% of human insulin+ cells. Interestingly, MAFA nuclear expression in both alpha and beta cells, and the percentage of alpha cells expressing PAX4 were found altered in a substantial proportion of patients with type 2 diabetes. Both MAFA and PAX4 display, therefore, a distinct expression pattern in human islet cells, suggesting more potential plasticity of human islets as compared with rodent islets.
Highlights
The development and functions of different types of islet cells are controlled, to a large extent, by essential cell-lineage-specific transcription factors
Protein extracts from mouse embryonic fibroblasts (MEF) transfected with empty pcDNA and pcDNA expressing respectively human MAFA and MAFB were used for the detection, using antibodies against MAFA (Abcam) or MAFB
Our present study revealed significantly different PAX4 and MAFA protein expression patterns in human islets compared to what was previously established in rodents
Summary
The development and functions of different types of islet cells are controlled, to a large extent, by essential cell-lineage-specific transcription factors. MafB is involved in embryonic development of both mouse pancreatic alpha and beta cells [5,6], whereas MafA participates mainly in the maturation of mouse beta cells [2]. We and others have recently demonstrated that MafB expression can be reactivated in mouse beta cells undergoing adaptive proliferation [7,8] and during tumorigenesis [7], indicating that the dynamic modulation of Maf expression could be involved in the control of beta cell proliferation and their endocrine functions. Based largely on the knowledge acquired from the above mentioned studies in the mouse, several strategies to cure diabetes are aimed at replenishing the pool of beta cells, by overexpressing beta cell specific transcription factors, including Pax, MafA and Pdx in different cell-types
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