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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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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 |
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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 |
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