title: MicroRNA expression in alpha and beta cells of human pancreatic islets.
abstract: microRNAs (miRNAs) play an important role in pancreatic development and adult β-cell physiology. Our hypothesis is based on the assumption that each islet cell type has a specific pattern of miRNA expression. We sought to determine the profile of miRNA expression in α-and β-cells, the main components of pancreatic islets, because this analysis may lead to a better understanding of islet gene regulatory pathways. Highly enriched (>98%) subsets of human α-and β-cells were obtained by flow cytometric sorting after intracellular staining with c-peptide and glucagon antibody. The method of sorting based on intracellular staining is possible because miRNAs are stable after fixation. MiRNA expression levels were determined by quantitative high throughput PCR-based miRNA array platform screening. Most of the miRNAs were preferentially expressed in β-cells. From the total of 667 miRNAs screened, the Significant Analysis of Microarray identified 141 miRNAs, of which only 7 were expressed more in α-cells (α-miRNAs) and 134 were expressed more in β-cells (β-miRNAs). Bioinformatic analysis identified potential targets of β-miRNAs analyzing the Beta Cell Gene Atlas, described in the T1Dbase, the web platform, supporting the type 1 diabetes (T1D) community. cMaf, a transcription factor regulating glucagon expression expressed selectively in α-cells (TFα) is targeted by β-miRNAs; miR-200c, miR-125b and miR-182. Min6 cells treated with inhibitors of these miRNAs show an increased expression of cMaf RNA. Conversely, over expression of miR-200c, miR-125b or miR-182 in the mouse alpha cell line αTC6 decreases the level of cMAF mRNA and protein. MiR-200c also inhibits the expression of Zfpm2, a TFα that inhibits the PI3K signaling pathway, at both RNA and protein levels.In conclusion, we identified miRNAs differentially expressed in pancreatic α- and β-cells and their potential transcription factor targets that could add new insights into different aspects of islet biology and pathophysiology.
authors: Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
authors: Dagmar
authors: D
authors: Klein
authors: Ryosuke
authors: R
authors: Misawa
authors: Valia
authors: V
authors: Bravo-Egana
authors: Nancy
authors: N
authors: Vargas
authors: Samuel
authors: S
authors: Rosero
authors: Julieta
authors: J
authors: Piroso
authors: Hirohito
authors: H
authors: Ichii
authors: Oliver
authors: O
authors: Umland
authors: Jiang
authors: J
authors: Zhijie
authors: Nicholas
authors: N
authors: Tsinoremas
authors: Camillo
authors: C
authors: Ricordi
authors: Luca
authors: L
authors: Inverardi
authors: Juan
authors: J
authors: Domínguez-Bendala
authors: Ricardo L
authors: RL
authors: Pastori
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D019295:Computational Biology; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051381:Rats; D059467:Transcriptome
chemical_list: D035683:MicroRNAs
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