Transcriptomic Network Interactions in Human Skin Treated with Topical Glucocorticoid Clobetasol Propionate.
Administration, Topical
Adult
Black or African American
Clobetasol
/ therapeutic use
Computational Biology
Female
Gene Knockdown Techniques
Gene Regulatory Networks
Glucocorticoids
/ therapeutic use
Humans
Interferons
/ genetics
Kruppel-Like Transcription Factors
/ genetics
Male
Middle Aged
STAT3 Transcription Factor
/ genetics
Sex Factors
Skin
/ drug effects
Skin Physiological Phenomena
Transcriptome
/ genetics
White People
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
12
11
2018
revised:
11
04
2019
accepted:
18
04
2019
pubmed:
28
6
2019
medline:
9
6
2020
entrez:
28
6
2019
Statut:
ppublish
Résumé
Glucocorticoids are the most frequently used anti-inflammatory drugs in dermatology. However, the molecular signature of glucocorticoids and their receptor in human skin is largely unknown. Our validated bioinformatics analysis of human skin transcriptome induced by topical glucocorticoid clobetasol propionate (CBP) in healthy volunteers identified numerous unreported glucocorticoid-responsive genes, including over a thousand noncoding RNAs. We observed sexual and racial dimorphism in the CBP response including a shift toward IFN-α/IFN-γ and IL-6/Jak/Signal transducer and activator of transcription (STAT) 3 signaling in female skin; and a larger response to CBP in African-American skin. Weighted gene coexpression network analysis unveiled a dense skin network of 41 transcription factors including circadian Kruppel-like factor 9 (KLF9), and ∼260 of their target genes enriched for functional pathways representative of the entire CBP transcriptome. Using keratinocytes with Kruppel-like factor 9 knockdown, we revealed a feedforward loop in glucocorticoid receptor signaling, previously unreported. Interestingly, many of the CBP-regulated transcription factors were involved in the control of development, metabolism, circadian clock; and 80% of them were associated with skin aging showing similarities between glucocorticoid-treated and aged skin. Overall, these findings indicate that glucocorticoid receptor acts as an important regulator of gene expression in skin-both at the transcriptional and posttranscriptional level-via multiple mechanisms including regulation of noncoding RNAs and multiple core transcription factors.
Identifiants
pubmed: 31247200
pii: S0022-202X(19)31629-X
doi: 10.1016/j.jid.2019.04.021
pmc: PMC6814545
mid: NIHMS1532721
pii:
doi:
Substances chimiques
Glucocorticoids
0
KLF9 protein, human
0
Kruppel-Like Transcription Factors
0
STAT3 Transcription Factor
0
Interferons
9008-11-1
Clobetasol
ADN79D536H
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2281-2291Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK098242
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR057216
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125366
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM112945
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075049
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
J Am Acad Dermatol. 2003 Jun;48(6 Suppl):S143-8
pubmed: 12789168
J Biol Chem. 1997 Dec 5;272(49):30607-10
pubmed: 9388192
Am J Physiol Endocrinol Metab. 2003 May;284(5):E855-62
pubmed: 12676647
Microbiol Mol Biol Rev. 2016 May 11;80(2):495-522
pubmed: 27169854
Dev Biol. 2008 Mar 15;315(2):459-73
pubmed: 18262513
Adv Exp Med Biol. 2015;872:179-215
pubmed: 26215995
Sci Rep. 2016 Feb 15;6:20975
pubmed: 26876687
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
BMC Genomics. 2014 Aug 06;15:656
pubmed: 25099603
Oncotarget. 2018 Oct 5;9(78):34772-34783
pubmed: 30410676
J Invest Dermatol. 2017 Jul;137(7):1474-1483
pubmed: 28259685
Pharmacol Ther. 2015 Aug;152:28-41
pubmed: 25958032
Mol Carcinog. 2007 Aug;46(8):732-40
pubmed: 17538956
EBioMedicine. 2019 Mar;41:526-537
pubmed: 30737086
Trends Endocrinol Metab. 2018 Jan;29(1):42-54
pubmed: 29162310
Genome Biol. 2013 Jul 26;14(7):R75
pubmed: 23889843
J Cell Biol. 2011 Apr 4;193(1):235-50
pubmed: 21464233
Nat Med. 2014 Sep;20(9):1043-9
pubmed: 25129481
J Biol Chem. 2007 Feb 9;282(6):4021-34
pubmed: 17095510
J Biol Chem. 2018 Jan 26;293(4):1439-1449
pubmed: 29158265
EMBO J. 2013 Oct 2;32(19):2548-60
pubmed: 23942238
J Clin Endocrinol Metab. 2010 Jan;95(1):246-55
pubmed: 19875485
J Am Acad Dermatol. 2005 Jul;53(1 Suppl 1):S50-8
pubmed: 15968264
J Pharmacol Pharmacother. 2016 Jan-Mar;7(1):1-5
pubmed: 27127387
Histochem Cell Biol. 2014 Mar;141(3):289-300
pubmed: 24186058
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):752-6
pubmed: 8290595
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Biol Chem. 2003 Oct 24;278(43):41779-88
pubmed: 12902338
Nucleic Acids Res. 2017 Jan 4;45(D1):D61-D67
pubmed: 27924024
Mediators Inflamm. 1998;7(3):183-93
pubmed: 9705606
EMBO Mol Med. 2014 Dec 11;7(1):42-58
pubmed: 25504525
Oncogene. 2007 Mar 22;26(13):1885-96
pubmed: 17016446
J Invest Dermatol. 2018 Sep;138(9):1935-1944
pubmed: 29596905
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Endocr Rev. 2005 Dec;26(7):898-915
pubmed: 16126938
Bioessays. 2013 Dec;35(12):1093-100
pubmed: 24115003
Science. 1992 May 29;256(5061):1315-8
pubmed: 1376003
Gene. 2018 Apr 15;650:19-26
pubmed: 29409992
N Engl J Med. 2005 Oct 20;353(16):1711-23
pubmed: 16236742
J Invest Dermatol. 2005 Dec;125(6):1163-73
pubmed: 16354186
J Cancer Prev. 2015 Dec;20(4):250-9
pubmed: 26734587
J Biol Chem. 1995 Sep 1;270(35):20479-84
pubmed: 7657624
Histochem Cell Biol. 2015 May;143(5):443-52
pubmed: 25514850
J Am Acad Dermatol. 1996 Aug;35(2 Pt 1):183-6
pubmed: 8708016
Eur J Endocrinol. 2012 Jun;166(6):1039-48
pubmed: 22450549
Skin Pharmacol Physiol. 2010;23(3):139-51
pubmed: 20051715
J Allergy Clin Immunol. 2013 Nov;132(5):1033-44
pubmed: 24084075
BMC Biol. 2017 Feb 7;15(1):7
pubmed: 28173793
Nucleic Acids Res. 2018 Jan 4;46(D1):D380-D386
pubmed: 29087512
Exp Dermatol. 2014 Oct;23(10):731-5
pubmed: 25055985
Cold Spring Harb Perspect Med. 2015 Jan 05;5(1):a015370
pubmed: 25561721
Mol Cell Endocrinol. 2007 Sep 15;275(1-2):109-17
pubmed: 17630119
Am J Clin Dermatol. 2017 Feb;18(1):67-75
pubmed: 27770310
J Allergy Clin Immunol. 2017 Mar;139(3):780-789
pubmed: 27484035
BMC Bioinformatics. 2008 Dec 29;9:559
pubmed: 19114008
Immunity. 2012 Apr 20;36(4):542-50
pubmed: 22520847
Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):10903-8
pubmed: 22711835
Genome Biol. 2017 Nov 15;18(1):220
pubmed: 29141660
J Am Med Assoc. 1952 Mar 15;148(11):904-7
pubmed: 14897683
PLoS One. 2007 Sep 19;2(9):e898
pubmed: 17878933
J Biol Chem. 2015 Mar 27;290(13):8348-59
pubmed: 25697355
Invest Ophthalmol Vis Sci. 2009 Feb;50(2):765-70
pubmed: 18936135
Oncotarget. 2018 Jan 1;9(26):18648-18663
pubmed: 29719633