Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts.
ERK1
ERK2
IGFBP5
mouse embryonic fibroblasts
replicative senescence
Journal
Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617
Informations de publication
Date de publication:
04 04 2022
04 04 2022
Historique:
received:
01
07
2021
accepted:
23
03
2022
pubmed:
5
4
2022
medline:
23
4
2022
entrez:
4
4
2022
Statut:
ppublish
Résumé
Insulin-like growth factor (IGF)-binding proteins (IGFBPs) are secretory proteins that regulate IGF signaling. In this study, we investigated the role of IGFBP5 in replicative senescence in embryonic mouse fibroblasts (MEFs). During passages according to the 3T3 method, MEFs underwent senescence after the 5th passage (P5) based on cell growth arrest, an increase in the number of cells positive for senescence-associated β-galactosidase (SA-β-GAL) staining, and upregulation of p16 and p19. In P8 MEFs, IGFBP5 mRNA level was markedly reduced compared with that in P2 MEFs. Downregulation of IGFBP5 via siRNA in P2 MEFs increased the number of SA-β-GAL-positive cells, upregulated p16 and p19, and inhibited cell growth. Incubation of MEFs with IGFBP5 during serial passage increased the cumulative population doubling and decreased SA-β-GAL positivity compared with those in vehicle-treated cells. IGFBP5 knockdown in P2 MEFs increased phosphorylation levels of ERK1 and ERK2. Silencing of ERK2, but not that of ERK1, blocked the increase in the number of SA-β-GAL-positive cells in IGFBP5-knockdown cells. The reduction in the cell number and upregulation of p16 and p21 in IGFBP5-knockdown cells were attenuated by ERK2 knockdown. Our results suggest that downregulation of IGFBP5 during serial passage contributes to replicative senescence via ERK2 in MEFs.
Identifiants
pubmed: 35378512
pii: 203999
doi: 10.18632/aging.203999
pmc: PMC9037271
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2966-2988Références
Nat Commun. 2018 Jul 2;9(1):2560
pubmed: 29967491
J Biol Chem. 1996 Nov 29;271(48):30322-5
pubmed: 8939990
Physiol Genomics. 2008 Feb 19;32(3):393-400
pubmed: 18073271
Genes Dev. 2007 Mar 1;21(5):525-30
pubmed: 17344414
Cell. 2013 Nov 21;155(5):1119-30
pubmed: 24238961
J Biol Chem. 2001 Dec 14;276(50):46961-7
pubmed: 11598109
Dev Cell. 2014 Dec 22;31(6):722-33
pubmed: 25499914
Cell Signal. 2013 Dec;25(12):2540-7
pubmed: 23993963
Front Endocrinol (Lausanne). 2020 Mar 03;11:100
pubmed: 32194505
FEBS J. 2015 Sep;282(18):3455-73
pubmed: 26094870
J Biol Chem. 2011 Jul 29;286(30):26860-72
pubmed: 21642427
Mech Ageing Dev. 2011 Oct;132(10):468-79
pubmed: 21820463
J Cell Biol. 1963 May;17:299-313
pubmed: 13985244
J Cell Mol Med. 2019 Sep;23(9):6368-6377
pubmed: 31290273
Mol Cell Biol. 1997 Sep;17(9):5598-611
pubmed: 9271435
Mol Biol Cell. 2007 Nov;18(11):4543-52
pubmed: 17804819
J Endocrinol. 1998 Nov;159(2):297-306
pubmed: 9795371
Oncogene. 2011 Sep 15;30(37):3907-17
pubmed: 21460855
Trends Biochem Sci. 2020 Jul;45(7):578-592
pubmed: 32531228
J Bone Miner Res. 1999 Dec;14(12):2150-8
pubmed: 10620075
PLoS One. 2012;7(4):e35460
pubmed: 22514746
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7812-6
pubmed: 11427735
Mol Endocrinol. 2006 Sep;20(9):2173-86
pubmed: 16675541
J Endocrinol. 2002 Mar;172(3):423-40
pubmed: 11874691
J Biol Chem. 2013 Feb 22;288(8):5963-72
pubmed: 23297412
Genes Dev. 2013 Apr 15;27(8):900-15
pubmed: 23599344
Cell Death Differ. 2005 Mar;12(3):213-23
pubmed: 15618969
Nature. 2003 Jan 9;421(6919):182-7
pubmed: 12483226
Cell Cycle. 2012 Feb 15;11(4):730-9
pubmed: 22374671
Nat Rev Drug Discov. 2017 Oct;16(10):718-735
pubmed: 28729727
Nature. 1993 Dec 2;366(6454):461-4
pubmed: 8247153
Int J Mol Med. 2019 Nov;44(5):1921-1931
pubmed: 31545483
Nat Med. 2018 Aug;24(8):1246-1256
pubmed: 29988130
Mol Cancer Ther. 2018 Sep;17(9):1973-1983
pubmed: 29925528
Aging (Albany NY). 2020 Apr 17;12(8):6823-6851
pubmed: 32302288
Elife. 2020 Mar 30;9:
pubmed: 32223893
Nucleic Acids Res. 2013 Jan 7;41(1):182-95
pubmed: 23143272
Oncogene. 2000 Mar 23;19(13):1698-709
pubmed: 10763827
Aging (Albany NY). 2019 May 13;11(9):2889-2897
pubmed: 31085799
J Biol Chem. 2006 May 19;281(20):14184-91
pubmed: 16543235
PLoS One. 2013 Jul 30;8(7):e69178
pubmed: 23935948
Nat Rev Cancer. 2010 Jan;10(1):51-7
pubmed: 20029423
Mol Cell Biol. 2008 Jan;28(1):511-27
pubmed: 17967895
Nat Rev Cancer. 2014 May;14(5):329-41
pubmed: 24722429
J Pharmacol Exp Ther. 2013 Jan;344(1):124-32
pubmed: 23042952
Biochem Biophys Res Commun. 2009 Aug 21;386(2):289-93
pubmed: 19465000
Nat Commun. 2021 Feb 1;12(1):720
pubmed: 33526781
Cell. 2015 Jul 2;162(1):72-83
pubmed: 26119340
Biomed Res Int. 2019 Nov 11;2019:3210324
pubmed: 31886201
Circ Res. 2004 Mar 19;94(5):E46-54
pubmed: 15001525
J Biol Chem. 2002 Jun 28;277(26):23172-80
pubmed: 11973331
Cell Death Dis. 2013 Nov 07;4:e911
pubmed: 24201810
Prog Growth Factor Res. 1995;6(2-4):465-73
pubmed: 8817691
EMBO J. 2004 Jan 14;23(1):212-20
pubmed: 14713953
Genes Dev. 1998 Oct 1;12(19):2997-3007
pubmed: 9765202
Free Radic Biol Med. 2008 May 15;44(10):1817-32
pubmed: 18329388
Front Cell Dev Biol. 2020 Mar 04;8:103
pubmed: 32195249
Stem Cell Res Ther. 2017 Sep 29;8(1):210
pubmed: 28962660
Nature. 1999 Jan 14;397(6715):164-8
pubmed: 9923679
Exp Cell Res. 1961 Dec;25:585-621
pubmed: 13905658
Nucleic Acids Res. 2020 Nov 4;48(19):10909-10923
pubmed: 33045748
Cancer Cell. 2008 Dec 9;14(6):458-70
pubmed: 19061837
Cancer Res. 2010 Apr 15;70(8):3013-9
pubmed: 20354179