title: Both PAX4 and MAFA are expressed in a substantial proportion of normal human pancreatic alpha cells and deregulated in patients with type 2 diabetes.
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.
authors.affiliation: Inserm U1052, Lyon, France ; CNRS UMR5286, Lyon, France ; Université de Lyon, Lyon, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Bonnavion
authors.forename: Rami
authors.initials: R
authors.lastname: Jaafar
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: Fouzia
authors.initials: F
authors.lastname: Assade
authors.forename: Esther
authors.initials: E
authors.lastname: van Stralen
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.forename: Célio
authors.initials: C
authors.lastname: Pouponnot
authors.forename: Sofia
authors.initials: S
authors.lastname: Gargani
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertolino
authors.forename: Martine
authors.initials: M
authors.lastname: Cordier-Bussat
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.forename: Chang Xian
authors.initials: CX
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology
chemical_list: D018398:Homeodomain Proteins; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors