Publication

Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts

Ong, J., Timens, W., Rajendran, V., Algra, A., Spira, A., Lenburg, M. E., Campbell, J. D., van den Berge, M., Postma, D. S., van den Berg, A., Kluiver, J. & Brandsma, C-A., 14-Sep-2017, In : PLoS ONE. 12, 9, 24 p., e0183815.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Ong, J., Timens, W., Rajendran, V., Algra, A., Spira, A., Lenburg, M. E., Campbell, J. D., van den Berge, M., Postma, D. S., van den Berg, A., Kluiver, J., & Brandsma, C-A. (2017). Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts. PLoS ONE, 12(9), [e0183815]. https://doi.org/10.1371/journal.pone.0183815

Author

Ong, Jennie ; Timens, Wim ; Rajendran, Vijay ; Algra, Arjan ; Spira, Avrum ; Lenburg, Marc E ; Campbell, Joshua D ; van den Berge, Maarten ; Postma, Dirkje S ; van den Berg, Anke ; Kluiver, Joost ; Brandsma, Corry-Anke. / Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts. In: PLoS ONE. 2017 ; Vol. 12, No. 9.

Harvard

Ong, J, Timens, W, Rajendran, V, Algra, A, Spira, A, Lenburg, ME, Campbell, JD, van den Berge, M, Postma, DS, van den Berg, A, Kluiver, J & Brandsma, C-A 2017, 'Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts', PLoS ONE, vol. 12, no. 9, e0183815. https://doi.org/10.1371/journal.pone.0183815

Standard

Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts. / Ong, Jennie; Timens, Wim; Rajendran, Vijay; Algra, Arjan; Spira, Avrum; Lenburg, Marc E; Campbell, Joshua D; van den Berge, Maarten; Postma, Dirkje S; van den Berg, Anke; Kluiver, Joost; Brandsma, Corry-Anke.

In: PLoS ONE, Vol. 12, No. 9, e0183815, 14.09.2017.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Ong J, Timens W, Rajendran V, Algra A, Spira A, Lenburg ME et al. Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts. PLoS ONE. 2017 Sep 14;12(9). e0183815. https://doi.org/10.1371/journal.pone.0183815


BibTeX

@article{5a83872a81d14c818b4958ef90a13767,
title = "Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts",
abstract = "BACKGROUND: Lung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling. Abnormal repair and remodeling has been observed in lung diseases like COPD. As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function.MATERIALS AND METHODS: We investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays. TGF-β1-induced miRNA expression changes were validated and replicated in an independent set of lung fibroblasts composted of 10 controls and 15 COPD patients using qRT-PCR. Ago2-immunoprecipitation followed by mRNA expression profiling was used to identify the miRNA-targetomes of unstimulated and TGF-β1-stimulated primary lung fibroblasts (n = 2). The genes affected by TGF-β1-modulated miRNAs were identified by comparing the miRNA targetomes of unstimulated and TGF-β1-stimulated fibroblasts.RESULTS: Twenty-nine miRNAs were significantly differentially expressed after TGF-β1 stimulation (FDR<0.05). The TGF-β1-induced miR-455-3p and miR-21-3p expression changes were validated and replicated, with in addition, lower miR-455-3p levels in COPD (p<0.05). We identified 964 and 945 genes in the miRNA-targetomes of unstimulated and TGF-β1-stimulated lung fibroblasts, respectively. The TGF-β and Wnt pathways were significantly enriched among the Ago2-IP enriched and predicted targets of miR-455-3p and miR-21-3p. The miR-455-3p target genes HN1, NGF, STRADB, DLD and ANO3 and the miR-21-3p target genes HHEX, CHORDC1 and ZBTB49 were consistently more enriched after TGF-β1 stimulation.CONCLUSION: Two miRNAs, miR-455-3p and miR-21-3p, were induced by TGF-β1 in lung fibroblasts. The significant Ago2-IP enrichment of targets of these miRNAs related to the TGF-β and/or Wnt pathways (NGF, DLD, HHEX) in TGF-β1-stimulated fibroblasts suggest a role for these miRNAs in lung diseases by affecting lung fibroblast function.",
keywords = "OBSTRUCTIVE PULMONARY-DISEASE, GENE-EXPRESSION, TISSUE-REPAIR, COPD, FIBROSIS, CANCER, INHIBITION, TARGETS, AIRWAY, CELLS",
author = "Jennie Ong and Wim Timens and Vijay Rajendran and Arjan Algra and Avrum Spira and Lenburg, {Marc E} and Campbell, {Joshua D} and {van den Berge}, Maarten and Postma, {Dirkje S} and {van den Berg}, Anke and Joost Kluiver and Corry-Anke Brandsma",
year = "2017",
month = sep,
day = "14",
doi = "10.1371/journal.pone.0183815",
language = "English",
volume = "12",
journal = "PLOS-One",
issn = "1932-6203",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "9",

}

RIS

TY - JOUR

T1 - Identification of transforming growth factorbeta-lregulated microRNAs and the microRNAtargetomes in primary lung fibroblasts

AU - Ong, Jennie

AU - Timens, Wim

AU - Rajendran, Vijay

AU - Algra, Arjan

AU - Spira, Avrum

AU - Lenburg, Marc E

AU - Campbell, Joshua D

AU - van den Berge, Maarten

AU - Postma, Dirkje S

AU - van den Berg, Anke

AU - Kluiver, Joost

AU - Brandsma, Corry-Anke

PY - 2017/9/14

Y1 - 2017/9/14

N2 - BACKGROUND: Lung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling. Abnormal repair and remodeling has been observed in lung diseases like COPD. As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function.MATERIALS AND METHODS: We investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays. TGF-β1-induced miRNA expression changes were validated and replicated in an independent set of lung fibroblasts composted of 10 controls and 15 COPD patients using qRT-PCR. Ago2-immunoprecipitation followed by mRNA expression profiling was used to identify the miRNA-targetomes of unstimulated and TGF-β1-stimulated primary lung fibroblasts (n = 2). The genes affected by TGF-β1-modulated miRNAs were identified by comparing the miRNA targetomes of unstimulated and TGF-β1-stimulated fibroblasts.RESULTS: Twenty-nine miRNAs were significantly differentially expressed after TGF-β1 stimulation (FDR<0.05). The TGF-β1-induced miR-455-3p and miR-21-3p expression changes were validated and replicated, with in addition, lower miR-455-3p levels in COPD (p<0.05). We identified 964 and 945 genes in the miRNA-targetomes of unstimulated and TGF-β1-stimulated lung fibroblasts, respectively. The TGF-β and Wnt pathways were significantly enriched among the Ago2-IP enriched and predicted targets of miR-455-3p and miR-21-3p. The miR-455-3p target genes HN1, NGF, STRADB, DLD and ANO3 and the miR-21-3p target genes HHEX, CHORDC1 and ZBTB49 were consistently more enriched after TGF-β1 stimulation.CONCLUSION: Two miRNAs, miR-455-3p and miR-21-3p, were induced by TGF-β1 in lung fibroblasts. The significant Ago2-IP enrichment of targets of these miRNAs related to the TGF-β and/or Wnt pathways (NGF, DLD, HHEX) in TGF-β1-stimulated fibroblasts suggest a role for these miRNAs in lung diseases by affecting lung fibroblast function.

AB - BACKGROUND: Lung fibroblasts are involved in extracellular matrix homeostasis, which is mainly regulated by transforming growth factor-beta (TGF-β), and are therefore crucial in lung tissue repair and remodeling. Abnormal repair and remodeling has been observed in lung diseases like COPD. As miRNA levels can be influenced by TGF-β, we hypothesized that TGF-β influences miRNA expression in lung fibroblasts, thereby affecting their function.MATERIALS AND METHODS: We investigated TGF-β1-induced miRNA expression changes in 9 control primary parenchymal lung fibroblasts using miRNA arrays. TGF-β1-induced miRNA expression changes were validated and replicated in an independent set of lung fibroblasts composted of 10 controls and 15 COPD patients using qRT-PCR. Ago2-immunoprecipitation followed by mRNA expression profiling was used to identify the miRNA-targetomes of unstimulated and TGF-β1-stimulated primary lung fibroblasts (n = 2). The genes affected by TGF-β1-modulated miRNAs were identified by comparing the miRNA targetomes of unstimulated and TGF-β1-stimulated fibroblasts.RESULTS: Twenty-nine miRNAs were significantly differentially expressed after TGF-β1 stimulation (FDR<0.05). The TGF-β1-induced miR-455-3p and miR-21-3p expression changes were validated and replicated, with in addition, lower miR-455-3p levels in COPD (p<0.05). We identified 964 and 945 genes in the miRNA-targetomes of unstimulated and TGF-β1-stimulated lung fibroblasts, respectively. The TGF-β and Wnt pathways were significantly enriched among the Ago2-IP enriched and predicted targets of miR-455-3p and miR-21-3p. The miR-455-3p target genes HN1, NGF, STRADB, DLD and ANO3 and the miR-21-3p target genes HHEX, CHORDC1 and ZBTB49 were consistently more enriched after TGF-β1 stimulation.CONCLUSION: Two miRNAs, miR-455-3p and miR-21-3p, were induced by TGF-β1 in lung fibroblasts. The significant Ago2-IP enrichment of targets of these miRNAs related to the TGF-β and/or Wnt pathways (NGF, DLD, HHEX) in TGF-β1-stimulated fibroblasts suggest a role for these miRNAs in lung diseases by affecting lung fibroblast function.

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - GENE-EXPRESSION

KW - TISSUE-REPAIR

KW - COPD

KW - FIBROSIS

KW - CANCER

KW - INHIBITION

KW - TARGETS

KW - AIRWAY

KW - CELLS

U2 - 10.1371/journal.pone.0183815

DO - 10.1371/journal.pone.0183815

M3 - Article

C2 - 28910321

VL - 12

JO - PLOS-One

JF - PLOS-One

SN - 1932-6203

IS - 9

M1 - e0183815

ER -

ID: 47990264