Both PAX4 and MAFA are expressed in a substantial proportion of normal human pancreatic alpha cells and deregulated in patients with type 2 diabetes

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 a...

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Published in:PloS one 2013-08, Vol.8 (8), p.e72194-e72194
Main Authors: Bonnavion, Rémy, Jaafar, Rami, Kerr-Conte, Julie, Assade, Fouzia, van Stralen, Esther, Leteurtre, Emmanuelle, Pouponnot, Célio, Gargani, Sofia, Pattou, François, Bertolino, Philippe, Cordier-Bussat, Martine, Lu, Jieli, Zhang, Chang Xian
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Animals
Antibodies
Beta cells
Case-Control Studies
Cell Nucleus - metabolism
Cells, Cultured
Deregulation
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - pathology
Female
Fibrosarcoma
Gene Expression
Gene Expression Regulation
Glucagon
Glucagon-Secreting Cells - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Homology
Hospitals
Humans
Insulin
Insulin-Secreting Cells - metabolism
Islet cells
Islets of Langerhans
Life sciences
Maf Transcription Factors, Large - genetics
Maf Transcription Factors, Large - metabolism
Male
Metabolism
Mice
Middle Aged
Mutation
Obesity - metabolism
Paired Box Transcription Factors - genetics
Paired Box Transcription Factors - metabolism
Pancreas
Pancreas - metabolism
Pancreas - pathology
Patients
Protein expression
Proteins
Rodents
Transcription factors
Transplants & implants
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0072194