Cargando…

Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism

OBJECTIVE: To investigate the expression of pancreatic microRNAs (miRNAs) during the period of perinatal beta-cell expansion and maturation in rats, determine the localization of these miRNAs and perform a pathway analysis with predicted target mRNAs expressed in perinatal pancreas. RESEARCH DESIGN...

Descripción completa

Detalles Bibliográficos
Autores principales: Larsen, Louise, Rosenstierne, Maiken W., Gaarn, Louise W., Bagge, Annika, Pedersen, Lykke, Dahmcke, Christina M., Nielsen, Jens H., Dalgaard, Louise T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191174/
https://www.ncbi.nlm.nih.gov/pubmed/22022489
http://dx.doi.org/10.1371/journal.pone.0025997
_version_ 1782213628000206848
author Larsen, Louise
Rosenstierne, Maiken W.
Gaarn, Louise W.
Bagge, Annika
Pedersen, Lykke
Dahmcke, Christina M.
Nielsen, Jens H.
Dalgaard, Louise T.
author_facet Larsen, Louise
Rosenstierne, Maiken W.
Gaarn, Louise W.
Bagge, Annika
Pedersen, Lykke
Dahmcke, Christina M.
Nielsen, Jens H.
Dalgaard, Louise T.
author_sort Larsen, Louise
collection PubMed
description OBJECTIVE: To investigate the expression of pancreatic microRNAs (miRNAs) during the period of perinatal beta-cell expansion and maturation in rats, determine the localization of these miRNAs and perform a pathway analysis with predicted target mRNAs expressed in perinatal pancreas. RESEARCH DESIGN AND METHODS: RNA was extracted from whole pancreas at embryonic day 20 (E20), on the day of birth (P0) and two days after birth (P2) and hybridized to miRNA microarrays. Differentially expressed miRNAs were verified by northern blotting and their pancreatic localization determined by in situ hybridization. Pathway analysis was done using regulated sets of mRNAs predicted as targets of the miRNAs. Possible target genes were tested using reporter-gene analysis in INS-1E cells. RESULTS: Nine miRNAs were differentially expressed perinatally, seven were confirmed to be regulated at the level of the mature miRNA. The localization studies showed endocrine localization of six of these miRNAs (miR-21, -23a, -29a, -125b-5p, -376b-3p and -451), and all were expressed in exocrine cells at one time point at least. Pathways involving metabolic processes, terpenoid and sterol metabolism were selectively affected by concomitant regulation by miRNAs and mRNAs, and Srebf1 was validated as a target of miR-21. CONCLUSIONS: The findings suggest that miRNAs are involved in the functional maturation of pancreatic exocrine and endocrine tissue following birth. Pathway analysis of target genes identify changes in sterol metabolism around birth as being selectively affected by differential miRNA expression during this period.
format Online
Article
Text
id pubmed-3191174
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-31911742011-10-21 Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism Larsen, Louise Rosenstierne, Maiken W. Gaarn, Louise W. Bagge, Annika Pedersen, Lykke Dahmcke, Christina M. Nielsen, Jens H. Dalgaard, Louise T. PLoS One Research Article OBJECTIVE: To investigate the expression of pancreatic microRNAs (miRNAs) during the period of perinatal beta-cell expansion and maturation in rats, determine the localization of these miRNAs and perform a pathway analysis with predicted target mRNAs expressed in perinatal pancreas. RESEARCH DESIGN AND METHODS: RNA was extracted from whole pancreas at embryonic day 20 (E20), on the day of birth (P0) and two days after birth (P2) and hybridized to miRNA microarrays. Differentially expressed miRNAs were verified by northern blotting and their pancreatic localization determined by in situ hybridization. Pathway analysis was done using regulated sets of mRNAs predicted as targets of the miRNAs. Possible target genes were tested using reporter-gene analysis in INS-1E cells. RESULTS: Nine miRNAs were differentially expressed perinatally, seven were confirmed to be regulated at the level of the mature miRNA. The localization studies showed endocrine localization of six of these miRNAs (miR-21, -23a, -29a, -125b-5p, -376b-3p and -451), and all were expressed in exocrine cells at one time point at least. Pathways involving metabolic processes, terpenoid and sterol metabolism were selectively affected by concomitant regulation by miRNAs and mRNAs, and Srebf1 was validated as a target of miR-21. CONCLUSIONS: The findings suggest that miRNAs are involved in the functional maturation of pancreatic exocrine and endocrine tissue following birth. Pathway analysis of target genes identify changes in sterol metabolism around birth as being selectively affected by differential miRNA expression during this period. Public Library of Science 2011-10-11 /pmc/articles/PMC3191174/ /pubmed/22022489 http://dx.doi.org/10.1371/journal.pone.0025997 Text en Larsen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Larsen, Louise
Rosenstierne, Maiken W.
Gaarn, Louise W.
Bagge, Annika
Pedersen, Lykke
Dahmcke, Christina M.
Nielsen, Jens H.
Dalgaard, Louise T.
Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism
title Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism
title_full Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism
title_fullStr Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism
title_full_unstemmed Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism
title_short Expression and Localization of microRNAs in Perinatal Rat Pancreas: Role of miR-21 in Regulation of Cholesterol Metabolism
title_sort expression and localization of micrornas in perinatal rat pancreas: role of mir-21 in regulation of cholesterol metabolism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191174/
https://www.ncbi.nlm.nih.gov/pubmed/22022489
http://dx.doi.org/10.1371/journal.pone.0025997
work_keys_str_mv AT larsenlouise expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism
AT rosenstiernemaikenw expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism
AT gaarnlouisew expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism
AT baggeannika expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism
AT pedersenlykke expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism
AT dahmckechristinam expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism
AT nielsenjensh expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism
AT dalgaardlouiset expressionandlocalizationofmicrornasinperinatalratpancreasroleofmir21inregulationofcholesterolmetabolism