Expression and localization of microRNAs in perinatal rat pancreas

role of miR-21 in regulation of cholesterol metabolism

Louise Larsen, Maiken Worsøe Rosenstierne, Louise Gaarn, Annika Bagge, Lykke Pedersen, Christina Mackeprang Dahmcke, Jens H. Nielsen, Louise Torp Dalgaard

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    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.
    OriginalsprogEngelsk
    TidsskriftP L o S One
    Vol/bind6
    Udgave nummer10
    Sider (fra-til)e25997
    Antal sider12
    ISSN1932-6203
    DOI
    StatusUdgivet - 11 okt. 2011

    Citer dette

    Larsen, Louise ; Rosenstierne, Maiken Worsøe ; Gaarn, Louise ; Bagge, Annika ; Pedersen, Lykke ; Dahmcke, Christina Mackeprang ; Nielsen, Jens H. ; Dalgaard, Louise Torp. / Expression and localization of microRNAs in perinatal rat pancreas : role of miR-21 in regulation of cholesterol metabolism. I: P L o S One. 2011 ; Bind 6, Nr. 10. s. e25997.
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    title = "Expression and localization of microRNAs in perinatal rat pancreas: role of miR-21 in regulation of cholesterol metabolism",
    abstract = "ABSTRACT 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.",
    keywords = "Pancreas, perinatal, microRNA, islets of Langerhans, beta-cell, gene expression, exocrine pancreas, ndocrine pancreas, cholesterol metabolism, mir-21, mir-29a",
    author = "Louise Larsen and Rosenstierne, {Maiken Wors{\o}e} and Louise Gaarn and Annika Bagge and Lykke Pedersen and Dahmcke, {Christina Mackeprang} and Nielsen, {Jens H.} and Dalgaard, {Louise Torp}",
    year = "2011",
    month = "10",
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    doi = "10.1371/journal.pone.0025997",
    language = "English",
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    pages = "e25997",
    journal = "P L o S One",
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    Expression and localization of microRNAs in perinatal rat pancreas : role of miR-21 in regulation of cholesterol metabolism. / Larsen, Louise; Rosenstierne, Maiken Worsøe; Gaarn, Louise; Bagge, Annika; Pedersen, Lykke; Dahmcke, Christina Mackeprang; Nielsen, Jens H.; Dalgaard, Louise Torp.

    I: P L o S One, Bind 6, Nr. 10, 11.10.2011, s. e25997.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Expression and localization of microRNAs in perinatal rat pancreas

    T2 - role of miR-21 in regulation of cholesterol metabolism

    AU - Larsen, Louise

    AU - Rosenstierne, Maiken Worsøe

    AU - Gaarn, Louise

    AU - Bagge, Annika

    AU - Pedersen, Lykke

    AU - Dahmcke, Christina Mackeprang

    AU - Nielsen, Jens H.

    AU - Dalgaard, Louise Torp

    PY - 2011/10/11

    Y1 - 2011/10/11

    N2 - ABSTRACT 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.

    AB - ABSTRACT 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.

    KW - Pancreas

    KW - perinatal

    KW - microRNA

    KW - islets of Langerhans

    KW - beta-cell

    KW - gene expression

    KW - exocrine pancreas

    KW - ndocrine pancreas

    KW - cholesterol metabolism

    KW - mir-21

    KW - mir-29a

    U2 - 10.1371/journal.pone.0025997

    DO - 10.1371/journal.pone.0025997

    M3 - Journal article

    VL - 6

    SP - e25997

    JO - P L o S One

    JF - P L o S One

    SN - 1932-6203

    IS - 10

    ER -