Time and phenotype-dependent transcriptome analysis in AAV-TGFβ1 and Bleomycin-induced lung fibrosis models.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 07 2022
16 07 2022
Historique:
received:
13
01
2022
accepted:
08
07
2022
entrez:
16
7
2022
pubmed:
17
7
2022
medline:
20
7
2022
Statut:
epublish
Résumé
We have previously established a novel mouse model of lung fibrosis based on Adeno-associated virus (AAV)-mediated pulmonary overexpression of TGFβ1. Here, we provide an in-depth characterization of phenotypic and transcriptomic changes (mRNA and miRNA) in a head-to-head comparison with Bleomycin-induced lung injury over a 4-week disease course. The analyses delineate the temporal state of model-specific and commonly altered pathways, thereby providing detailed insights into the processes underlying disease development. They further guide appropriate model selection as well as interventional study design. Overall, Bleomycin-induced fibrosis resembles a biphasic process of acute inflammation and subsequent transition into fibrosis (with partial resolution), whereas the TGFβ1-driven model is characterized by pronounced and persistent fibrosis with concomitant inflammation and an equally complex disease phenotype as observed upon Bleomycin instillation. Finally, based on an integrative approach combining lung function data, mRNA/miRNA profiles, their correlation and miRNA target predictions, we identify putative drug targets and miRNAs to be explored as therapeutic candidates for fibrotic diseases. Taken together, we provide a comprehensive analysis and rich data resource based on RNA-sequencing, along with a strategy for transcriptome-phenotype coupling. The results will be of value for TGFβ research, drug discovery and biomarker identification in progressive fibrosing interstitial lung diseases.
Identifiants
pubmed: 35842487
doi: 10.1038/s41598-022-16344-7
pii: 10.1038/s41598-022-16344-7
pmc: PMC9288451
doi:
Substances chimiques
MicroRNAs
0
RNA, Messenger
0
Bleomycin
11056-06-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12190Informations de copyright
© 2022. The Author(s).
Références
Mol Ther. 2015 Oct;23(10):1582-91
pubmed: 26137851
J Biol Chem. 1989 Aug 15;264(23):13660-4
pubmed: 2474534
Clin Exp Immunol. 2003 Apr;132(1):1-8
pubmed: 12653829
Lab Invest. 2017 Sep;97(9):1020-1032
pubmed: 28737764
EMBO Mol Med. 2014 Sep 19;6(10):1347-56
pubmed: 25239947
BMC Bioinformatics. 2008 Dec 29;9:559
pubmed: 19114008
Am J Respir Cell Mol Biol. 2021 Apr;64(4):453-464
pubmed: 33493091
Nat Commun. 2020 Apr 21;11(1):1920
pubmed: 32317643
Nat Immunol. 2019 Feb;20(2):163-172
pubmed: 30643263
Nucleic Acids Res. 2019 Jan 8;47(D1):D155-D162
pubmed: 30423142
Am J Respir Cell Mol Biol. 2018 Sep;59(3):295-305
pubmed: 29652518
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Dis Model Mech. 2014 Feb;7(2):193-203
pubmed: 24713275
J Pathol. 2021 Feb;253(2):186-197
pubmed: 33095908
J Clin Pathol. 1988 Apr;41(4):467-70
pubmed: 3366935
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6292-7
pubmed: 11983918
Front Mol Biosci. 2020 Jul 14;7:138
pubmed: 32760736
J Pharmacol Exp Ther. 2005 Jun;313(3):943-51
pubmed: 15769863
Mol Syst Biol. 2015 Jul 14;11(7):819
pubmed: 26174933
J Exp Med. 2010 Aug 2;207(8):1589-97
pubmed: 20643828
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
Gene Ther. 2003 Dec;10(26):2112-8
pubmed: 14625565
Cell Rep. 2018 Mar 27;22(13):3625-3640
pubmed: 29590628
Am J Respir Cell Mol Biol. 2019 Jul;61(1):74-85
pubmed: 30848683
Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1255-62
pubmed: 12857673
Cell Rep. 2020 Nov 10;33(6):108356
pubmed: 33176144
Nucleic Acids Res. 2014;42(17):e133
pubmed: 25063298
Br J Pharmacol. 2017 Nov;174(21):3848-3864
pubmed: 28810065
Nat Commun. 2020 Jul 16;11(1):3559
pubmed: 32678092
Thorax. 2007 Nov;62(11):1008-12
pubmed: 17965079
J Pathol. 2015 Jul;236(3):384-94
pubmed: 25779936
Nat Protoc. 2012 Mar 01;7(3):562-78
pubmed: 22383036
Mucosal Immunol. 2009 Mar;2(2):103-21
pubmed: 19129758
Int J Mol Med. 2021 Dec;48(6):
pubmed: 34651657
Nat Commun. 2019 Feb 27;10(1):963
pubmed: 30814501
Ageing Res Rev. 2021 Sep;70:101405
pubmed: 34242806
Immunity. 2015 Feb 17;42(2):332-343
pubmed: 25692705
Am J Respir Cell Mol Biol. 2019 Jun;60(6):705-716
pubmed: 30742493
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Am J Respir Crit Care Med. 2019 Mar 1;199(5):622-630
pubmed: 30141961
PLoS One. 2013;8(4):e59348
pubmed: 23565148
J Cancer Res Clin Oncol. 2019 Sep;145(9):2285-2292
pubmed: 31372722
Gene. 2015 May 10;562(1):138-44
pubmed: 25725128
EMBO Rep. 2021 Aug 4;22(8):e52785
pubmed: 34224201
Hum Gene Ther Methods. 2015 Aug;26(4):147-57
pubmed: 26222983
ACS Synth Biol. 2020 Jun 19;9(6):1292-1305
pubmed: 32427483
Gastroenterology. 2012 Mar;142(3):612-621.e5
pubmed: 22138190
Nucleic Acids Res. 2020 Jan 8;48(D1):D498-D503
pubmed: 31691815
BMJ Open Respir Res. 2017 Sep 17;4(1):e000212
pubmed: 29018526
Genome Biol. 2014 Mar 03;15(3):R46
pubmed: 24580807
Am J Respir Cell Mol Biol. 2009 Jul;41(1):85-92
pubmed: 19097987
Nature. 2018 Aug;560(7718):377-381
pubmed: 30069046
J Immunol. 2011 Nov 15;187(10):5336-45
pubmed: 22013119
Thorax. 2009 Dec;64(12):1053-61
pubmed: 19850962
Nat Commun. 2018 Aug 1;9(1):3016
pubmed: 30069061
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
J Cell Sci. 2018 Mar 2;131(5):
pubmed: 29440237
Am J Respir Cell Mol Biol. 2011 Aug;45(2):287-94
pubmed: 20971881
Front Med (Lausanne). 2018 Apr 04;5:87
pubmed: 29670881
Curr Top Dev Biol. 2016;116:231-45
pubmed: 26970622
J Clin Invest. 1997 Aug 15;100(4):768-76
pubmed: 9259574
Cell Physiol Biochem. 2011;28(3):571-8
pubmed: 22116372
Am J Respir Cell Mol Biol. 2015 Sep;53(3):291-302
pubmed: 25845025
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
BMC Bioinformatics. 2016 Oct 21;17(1):428
pubmed: 27769170
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761
pubmed: 29155950
Int J Mol Sci. 2021 Jun 29;22(13):
pubmed: 34209809
Am J Respir Cell Mol Biol. 2015 Feb;52(2):217-31
pubmed: 25029475
Cold Spring Harb Perspect Biol. 2017 Jun 1;9(6):
pubmed: 28108486
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
J Exp Med. 2011 Jul 4;208(7):1339-50
pubmed: 21727191
PLoS Genet. 2013;9(2):e1003291
pubmed: 23459460
Front Pharmacol. 2014 Jan 10;4:173
pubmed: 24454287
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
pubmed: 10592173
Eur Respir J. 2015 May;45(5):1434-45
pubmed: 25745043
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Cardiovasc Pathol. 2018 Jul - Aug;35:12-19
pubmed: 29729633
Sci Rep. 2018 Nov 8;8(1):16571
pubmed: 30410021
Mol Ther. 2016 Oct;24(10):1734-1744
pubmed: 27350126
N Engl J Med. 2011 Apr 21;364(16):1503-12
pubmed: 21506741
Sci Rep. 2017 Dec;7(1):149
pubmed: 28273952
PLoS One. 2014 Oct 13;9(10):e108528
pubmed: 25310401
Dis Model Mech. 2022 Jan 1;15(1):
pubmed: 34845494
J Transl Med. 2008 Apr 10;6:16
pubmed: 18402687
Nature. 2018 Aug;560(7718):319-324
pubmed: 30069044
Nat Commun. 2018 Apr 10;9(1):1366
pubmed: 29636450
Nat Rev Drug Discov. 2015 Oct;14(10):693-720
pubmed: 26338155
Hum Gene Ther. 2007 Aug;18(8):753-62
pubmed: 17685831
Nat Med. 2012 Jul 06;18(7):1028-40
pubmed: 22772564
Free Radic Biol Med. 2010 Jan 1;48(1):1-15
pubmed: 19800967