The microRNA-34a-Induced Senescence-Associated Secretory Phenotype (SASP) Favors Vascular Smooth Muscle Cells Calcification.
Adult
Aged
Aged, 80 and over
Animals
Cell Differentiation
Cell Proliferation
Cells, Cultured
Cellular Senescence
Female
Healthy Volunteers
Humans
Interleukin-6
/ genetics
Male
Mice
Mice, Inbred C57BL
MicroRNAs
/ genetics
Middle Aged
Muscle, Smooth, Vascular
/ metabolism
Vascular Calcification
/ genetics
Young Adult
IL6
SASP
VSMCs
inflammaging
senescence
vascular calcification
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
23 Jun 2020
23 Jun 2020
Historique:
received:
11
05
2020
revised:
17
06
2020
accepted:
19
06
2020
entrez:
27
6
2020
pubmed:
27
6
2020
medline:
23
3
2021
Statut:
epublish
Résumé
The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J
Identifiants
pubmed: 32585876
pii: ijms21124454
doi: 10.3390/ijms21124454
pmc: PMC7352675
pii:
doi:
Substances chimiques
Interleukin-6
0
MIRN34 microRNA, human
0
MIRN34a microRNA, mouse
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
Aging (Albany NY). 2016 Jul;8(7):1316-29
pubmed: 27288264
Aging (Albany NY). 2020 Jan 17;12(2):1987-2004
pubmed: 31951594
Aging (Albany NY). 2011 Oct;3(10):985-1002
pubmed: 22064828
Circ Res. 2013 May 10;112(10):e99-109
pubmed: 23564641
Genes Dev. 2014 Jan 15;28(2):99-114
pubmed: 24449267
Circulation. 2003 Jan 7;107(1):139-46
pubmed: 12515756
Ageing Res Rev. 2009 Jan;8(1):18-30
pubmed: 18692159
Aging Cell. 2019 Jun;18(3):e12918
pubmed: 30848072
Semin Immunol. 2018 Dec;40:17-35
pubmed: 30287177
Biochim Biophys Acta Mol Basis Dis. 2019 Jul 1;1865(7):1810-1821
pubmed: 31109451
Trends Endocrinol Metab. 2014 Feb;25(2):72-9
pubmed: 24365513
EMBO Mol Med. 2013 Feb;5(2):180-90
pubmed: 23339066
Arterioscler Thromb Vasc Biol. 2019 Mar;39(3):432-445
pubmed: 30626205
Arch Immunol Ther Exp (Warsz). 2016 Apr;64(2):111-26
pubmed: 26658771
Life Sci. 1992;51(25):1953-6
pubmed: 1453878
Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1673-84
pubmed: 19749165
Arterioscler Thromb Vasc Biol. 2012 Jan;32(1):103-9
pubmed: 22034510
Aging Cell. 2007 Aug;6(4):535-45
pubmed: 17635417
J Cell Mol Med. 2019 May;23(5):3538-3548
pubmed: 30793480
Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E110-6
pubmed: 20424141
Mediators Inflamm. 2018 Apr 17;2018:9076485
pubmed: 29849499
Biochem Biophys Res Commun. 2010 Aug 6;398(4):735-40
pubmed: 20627091
Circulation. 2010 May 25;121(20):2200-10
pubmed: 20458013
J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1304-11
pubmed: 25352462
Arterioscler Thromb Vasc Biol. 2015 Sep;35(9):1963-74
pubmed: 26139463
J Gerontol A Biol Sci Med Sci. 2012 Aug;67(8):811-20
pubmed: 22219513
J Clin Invest. 2013 Mar;123(3):966-72
pubmed: 23454759
Bone. 2019 Jul;124:53-61
pubmed: 30981888
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12052-7
pubmed: 22778398
Aging (Albany NY). 2019 Mar 23;11(6):1648-1663
pubmed: 30903794
PLoS One. 2015 Jan 30;10(1):e0116480
pubmed: 25635860
Cell. 2009 Jan 23;136(2):215-33
pubmed: 19167326
Nature. 2013 Mar 7;495(7439):107-10
pubmed: 23426265
Int J Mol Sci. 2019 Nov 14;20(22):
pubmed: 31739395
Circ Res. 2011 Apr 15;108(8):917-28
pubmed: 21350216
Kidney Int. 2019 Apr;95(4):958-972
pubmed: 30827513
J Physiol. 2016 Apr 15;594(8):2085-94
pubmed: 26040259
Circ Res. 2007 Mar 2;100(4):502-9
pubmed: 17255529
Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2079-2090
pubmed: 30026277
Cardiovasc Res. 2018 Mar 15;114(4):590-600
pubmed: 29514202
Ann N Y Acad Sci. 2000 Jun;908:244-54
pubmed: 10911963
Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):2054-62
pubmed: 21719763