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

Rémy Bonnavion; Rami Jaafar; Julie Kerr-Conte; Fouzia Assade; Esther van Stralen; Emmanuelle Leteurtre; Célio Pouponnot; Sofia Gargani; François Pattou; Philippe Bertolino; Martine Cordier-Bussat; Jieli Lu; Chang Xian Zhang

doi:10.1371/journal.pone.0072194

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

PLoS One. 2013 Aug 27;8(8):e72194. doi: 10.1371/journal.pone.0072194. eCollection 2013.

Authors

Rémy Bonnavion¹, Rami Jaafar, Julie Kerr-Conte, Fouzia Assade, Esther van Stralen, Emmanuelle Leteurtre, Célio Pouponnot, Sofia Gargani, François Pattou, Philippe Bertolino, Martine Cordier-Bussat, Jieli Lu, Chang Xian Zhang

Affiliation

¹ Inserm U1052, Lyon, France ; CNRS UMR5286, Lyon, France ; Université de Lyon, Lyon, France.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Animals
Case-Control Studies
Cell Nucleus / metabolism
Cells, Cultured
Diabetes Mellitus, Type 2 / metabolism*
Diabetes Mellitus, Type 2 / pathology
Female
Gene Expression
Gene Expression Regulation
Glucagon-Secreting Cells / metabolism*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Insulin-Secreting Cells / metabolism
Maf Transcription Factors, Large / genetics
Maf Transcription Factors, Large / metabolism*
Male
Mice
Middle Aged
Obesity / metabolism
Paired Box Transcription Factors / genetics
Paired Box Transcription Factors / metabolism*
Pancreas / metabolism
Pancreas / pathology

Substances

Homeodomain Proteins
MAFA protein, human
Maf Transcription Factors, Large
PAX4 protein, human
Paired Box Transcription Factors

Grants and funding

This study was supported by the Fondation ARC pour la recherche sur le cancer, France (SFI20101201530); the Ligue contre le Cancer du Rhône (to CXZ) and de la Loire (to PB); Agence National de Recherche (grant SVSE2 ANR 10 BLAN 1240 04), the CMIRA program of Region Rhône-Alpes (12004959-01); National Nature Science Foundation of China (NSFC30900700, 81170719) and Shanghai New Excellent Youth Program (XYQ2011009). R. Bonnavion was the recipient of a PhD-fellowship from French Ministry of Higher Education and Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.