Nicotine Modulates Growth Factors and MicroRNA to Promote Inflammatory and Fibrotic Processes.
Animals
Cells, Cultured
Dose-Response Relationship, Drug
Humans
Inflammation Mediators
/ metabolism
Intercellular Signaling Peptides and Proteins
/ agonists
Male
MicroRNAs
/ antagonists & inhibitors
Nicotine
/ toxicity
Nicotinic Agonists
/ toxicity
Pulmonary Fibrosis
/ chemically induced
Rats
Rats, Inbred F344
Respiratory Mucosa
/ drug effects
Journal
The Journal of pharmacology and experimental therapeutics
ISSN: 1521-0103
Titre abrégé: J Pharmacol Exp Ther
Pays: United States
ID NLM: 0376362
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
05
08
2018
accepted:
01
11
2018
pubmed:
18
11
2018
medline:
5
11
2019
entrez:
18
11
2018
Statut:
ppublish
Résumé
Idiopathic pulmonary fibrosis (IPF) is a fatal disease that destroys the structure and function of the lungs. Risk factors include advanced age and genetic predisposition. However, tobacco use is the chief modifiable risk factor. The prevalence of tobacco use in IPF reaches up to 80%. Although tobacco smoke contains over 5000 chemicals, nicotine is a major component. Nicotine is a bioactive molecule that acts upon nicotinic acetylcholine receptors expressed on neuronal and non-neuronal cells including endothelial cells. Accordingly, it has a pleiotropic effect on cell proliferation and angiogenesis. The angiogenic effect is partly mediated by stimulation of growth factors including fibroblast, platelet-derived, and vascular endothelial growth factors. Nintedanib, a Food and Drug Administration-approved drug for IPF, works by inhibiting receptors for these growth factors, suggesting a pathobiologic role of the growth factors in IPF and a potential mechanism by which tobacco use may exacerbate the disease process; additionally, nicotine downregulates anti-inflammatory microRNAs (miRs) in lung cells. Here, we profiled the expression of miRs in lung tissues explanted from a lung injury model and examined the effect of nicotine on one of the identified miRs (miR-24) and its downstream targets. Our data show that miR-24 is downregulated during lung injury and is suppressed by nicotine. We also found that nicotine upregulates the expression of inflammatory cytokines targeted by miR-24. Finally, nicotine stimulated growth factors, fibroblast proliferation, collagen release, and expression of myofibroblast markers. Taken together, nicotine, alone or as a component of tobacco smoke, may accelerate the disease process in IPF through stimulation of growth factors and downregulation of anti-inflammatory miRs.
Identifiants
pubmed: 30446578
pii: jpet.118.252650
doi: 10.1124/jpet.118.252650
pmc: PMC6323623
doi:
Substances chimiques
Inflammation Mediators
0
Intercellular Signaling Peptides and Proteins
0
MIRN24 microRNA, rat
0
MicroRNAs
0
Nicotinic Agonists
0
Nicotine
6M3C89ZY6R
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
169-178Subventions
Organisme : NHLBI NIH HHS
ID : K01 HL118683
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137703
Pays : United States
Informations de copyright
Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.
Références
J Dent Res. 2010 Jan;89(1):34-9
pubmed: 19966042
Wiley Interdiscip Rev Dev Biol. 2015 May-Jun;4(3):215-66
pubmed: 25772309
Histochem Cell Biol. 2008 Aug;130(2):219-34
pubmed: 18566825
Lancet Respir Med. 2014 Jul;2(7):566-72
pubmed: 24875841
WormBook. 2005 Sep 21;:1-9
pubmed: 18050425
Eur Respir Rev. 2015 Sep;24(137):428-35
pubmed: 26324804
Respir Res. 2017 Jun 2;18(1):115
pubmed: 28576119
Anticancer Agents Med Chem. 2007 Jul;7(4):461-6
pubmed: 17630920
Br J Pharmacol. 2003 Mar;138(6):1037-48
pubmed: 12684259
Am J Pathol. 2009 Nov;175(5):1868-82
pubmed: 19808646
Br J Dermatol. 2010 Apr;162(4):717-23
pubmed: 19995368
Curr Drug Targets. 2012 May;13(5):666-70
pubmed: 22300033
J Clin Invest. 2001 Jun;107(12):1529-36
pubmed: 11413160
Thorax. 1988 Jul;43(7):516-24
pubmed: 2850637
Thorax. 2017 May;72(5):481-484
pubmed: 28070014
FASEB J. 2013 Jun;27(6):2382-91
pubmed: 23457217
J Cell Physiol. 2014 Jan;229(1):79-89
pubmed: 23765240
Am J Physiol Lung Cell Mol Physiol. 2016 Feb 1;310(3):L232-9
pubmed: 26608528
J Clin Invest. 1999 Mar;103(5):637-47
pubmed: 10074480
Am J Respir Cell Mol Biol. 2011 Nov;45(5):931-7
pubmed: 21454804
Thorax. 2013 Jul;68(7):605-8
pubmed: 23462155
Am J Physiol Lung Cell Mol Physiol. 2015 Aug 1;309(3):L293-304
pubmed: 26024894
Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L323-33
pubmed: 17215434
Am J Respir Cell Mol Biol. 2002 Jan;26(1):31-41
pubmed: 11751201
Respirology. 2016 Jan;21(1):57-64
pubmed: 26138798
Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4099-104
pubmed: 23431157
Pulm Med. 2012;2012:808260
pubmed: 22448328
Respir Res. 2002;3:13
pubmed: 11806848
Am J Respir Cell Mol Biol. 2012 Dec;47(6):879-87
pubmed: 23043088
Acta Med Croatica. 1995;49(4-5):187-93
pubmed: 8630452
Eur Respir J. 2001 Jan;17(1):122-32
pubmed: 11307741
Mol Cell Biochem. 2007 Mar;297(1-2):93-9
pubmed: 17021677
Transl Res. 2011 Apr;157(4):191-9
pubmed: 21420029
Cardiovasc Res. 2009 Aug 1;83(3):465-72
pubmed: 19398468
J Clin Med. 2016 Apr 11;5(4):
pubmed: 27077889
Am J Pathol. 2002 Feb;160(2):413-8
pubmed: 11839560
Am J Physiol Lung Cell Mol Physiol. 2012 Oct 15;303(8):L627-33
pubmed: 22904168
Curr Opin Pharmacol. 2014 Jun;16:43-9
pubmed: 24681350
Cell. 1993 Dec 3;75(5):843-54
pubmed: 8252621
J Leukoc Biol. 2016 Nov;100(5):1105-1112
pubmed: 27312847
Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):106-12
pubmed: 17082486
FASEB J. 2012 Dec;26(12):4778-87
pubmed: 22906950
Am J Pathol. 2012 Feb;180(2):484-93
pubmed: 22189082
Psychopharmacology (Berl). 2007 Feb;190(3):269-319
pubmed: 16896961
Drugs. 1999;59 Spec No:11-5
pubmed: 10548387
Am J Respir Cell Mol Biol. 2014 Mar;50(3):471-82
pubmed: 24111585
Surgery. 2000 Mar;127(3):316-22
pubmed: 10715988
Respir Res. 2015 Jul 03;16:83
pubmed: 26138239
Eur Respir J. 2012 Feb;39(2):419-28
pubmed: 21778164
Biochem Biophys Res Commun. 2012 Jan 6;417(1):17-22
pubmed: 22108052
Nat Commun. 2014 Oct 31;5:5214
pubmed: 25358394
Scand J Immunol. 2015 Feb;81(2):110-20
pubmed: 25418282
J Exp Med. 2010 Mar 15;207(3):535-52
pubmed: 20176803
J Vasc Surg. 1996 Dec;24(6):927-34; discussion 934-5
pubmed: 8976346
Respir Res. 2004 Dec 10;5:27
pubmed: 15588326
N Engl J Med. 2014 May 29;370(22):2071-82
pubmed: 24836310
Mol Cell Neurosci. 2015 Sep;68:340-9
pubmed: 26365992
Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L611-8
pubmed: 17545491
Antioxid Redox Signal. 2008 Feb;10(2):287-301
pubmed: 17961066
Trends Cardiovasc Med. 2008 Oct;18(7):247-53
pubmed: 19232953
Biochim Biophys Acta. 2013 Jul;1832(7):1028-40
pubmed: 23219955
Int J Clin Exp Pathol. 2014 Jan 15;7(2):552-64
pubmed: 24551275
J Clin Invest. 1990 Oct;86(4):1055-64
pubmed: 2170444
Am J Respir Crit Care Med. 2001 Sep 15;164(6):989-94
pubmed: 11587984
J Chronic Dis. 1983;36(6):439-49
pubmed: 6863468
Am J Pathol. 2005 May;166(5):1321-32
pubmed: 15855634
Mol Pharmacol. 1998 Nov;54(5):779-88
pubmed: 9804613
Am J Respir Crit Care Med. 2010 Jul 15;182(2):220-9
pubmed: 20395557
Nat Med. 2001 Jul;7(7):833-9
pubmed: 11433349
J Transl Med. 2015 Aug 01;13:249
pubmed: 26231702
Front Pharmacol. 2014 May 27;5:123
pubmed: 24904424
Am J Physiol Lung Cell Mol Physiol. 2015 Jul 15;309(2):L175-87
pubmed: 25979079
EMBO Mol Med. 2014 Sep 19;6(10):1347-56
pubmed: 25239947
Transl Res. 2015 Jan;165(1):48-60
pubmed: 24746870
Am J Respir Crit Care Med. 2015 Jul 15;192(2):e3-19
pubmed: 26177183
Sci Transl Med. 2014 Jun 11;6(240):240ra76
pubmed: 24920662
Int J Environ Res Public Health. 2011 Feb;8(2):613-28
pubmed: 21556207
Thorax. 2015 Nov;70(11):1092-4
pubmed: 26130332
Proc Am Thorac Soc. 2006 Jun;3(4):364-72
pubmed: 16738202
PLoS One. 2006 Dec 27;1:e108
pubmed: 17205112
Am J Respir Crit Care Med. 2017 Aug 15;196(4):409-411
pubmed: 28809513
BMC Med. 2015 Sep 24;13:176
pubmed: 26400687
Front Biosci (Landmark Ed). 2012 Jun 01;17:2667-74
pubmed: 22652804
Pulm Med. 2011;2011:461439
pubmed: 21766018
Clin Chest Med. 2012 Mar;33(1):165-78
pubmed: 22365253
Heart. 2007 Sep;93(9):1056-63
pubmed: 17395670
Biochem Cell Biol. 2015 Apr;93(2):129-37
pubmed: 25557625
Physiology (Bethesda). 2014 May;29(3):177-85
pubmed: 24789982
Drug Discov Today Dis Models. 2013 Fall;10(3):e145-e151
pubmed: 25328532