Probing tissue transglutaminase mediated vascular smooth muscle cell aging using a novel transamidation-deficient Tgm2-C277S mouse model.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
29 Jul 2021
29 Jul 2021
Historique:
received:
30
12
2020
accepted:
29
05
2021
revised:
21
05
2021
entrez:
30
7
2021
pubmed:
31
7
2021
medline:
31
7
2021
Statut:
epublish
Résumé
Tissue transglutaminase (TG2), a multifunctional protein of the transglutaminase family, has putative transamidation-independent functions in aging-associated vascular stiffening and dysfunction. Developing preclinical models will be critical to fully understand the physiologic relevance of TG2's transamidation-independent activity and to identify the specific function of TG2 for therapeutic targeting. Therefore, in this study, we harnessed CRISPR-Cas9 gene editing technology to introduce a mutation at cysteine 277 in the active site of the mouse Tgm2 gene. Heterozygous and homozygous Tgm2-C277S mice were phenotypically normal and were born at the expected Mendelian frequency. TG2 protein was ubiquitously expressed in the Tgm2-C277S mice at levels similar to those of wild-type (WT) mice. In the Tgm2-C277S mice, TG2 transglutaminase function was successfully obliterated, but the transamidation-independent functions ascribed to GTP, fibronectin, and integrin binding were preserved. In vitro, a remodeling stimulus led to the significant loss of vascular compliance in WT mice, but not in the Tgm2-C277S or TG2
Identifiants
pubmed: 34326316
doi: 10.1038/s41420-021-00543-8
pii: 10.1038/s41420-021-00543-8
pmc: PMC8322091
doi:
Types de publication
Journal Article
Langues
eng
Pagination
197Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL145132
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : R01HL148112
Informations de copyright
© 2021. The Author(s).
Références
Br J Pharmacol. 2016 Mar;173(5):839-55
pubmed: 26603619
Am J Physiol Heart Circ Physiol. 2013 Sep 15;305(6):H803-10
pubmed: 23873798
Am J Respir Crit Care Med. 2011 Sep 15;184(6):699-707
pubmed: 21700912
Circ Res. 2006 Jul 7;99(1):86-92
pubmed: 16741156
Cells Tissues Organs. 2014;200(2):104-17
pubmed: 25924936
Cardiovasc Res. 2018 Mar 15;114(4):513-528
pubmed: 29514201
PLoS One. 2009 May 25;4(5):e5682
pubmed: 19479059
Hypertension. 2015 Apr;65(4):698-703
pubmed: 25667214
Am J Physiol Heart Circ Physiol. 2012 Apr 1;302(7):H1355-66
pubmed: 22307675
J Atheroscler Thromb. 2005;12(3):138-42
pubmed: 16020913
Blood. 2001 Sep 1;98(5):1567-76
pubmed: 11520809
Hypertens Res. 2020 Nov;43(11):1175-1181
pubmed: 32409775
Biochem J. 1999 Nov 1;343 Pt 3:541-9
pubmed: 10527931
J Biol Chem. 1990 Nov 5;265(31):18944-51
pubmed: 2172239
PLoS One. 2009 Jul 01;4(7):e6123
pubmed: 19568436
Exp Cell Res. 2000 Aug 25;259(1):158-66
pubmed: 10942588
J Am Heart Assoc. 2014 Apr 10;3(2):e000599
pubmed: 24721796
J Biol Chem. 2001 Feb 23;276(8):5591-7
pubmed: 11087745
Biomaterials. 2005 Nov;26(33):6518-29
pubmed: 15927250
J Am Heart Assoc. 2017 Feb 3;6(2):
pubmed: 28159817
Breast Cancer Res. 2012 Jan 06;14(1):R4
pubmed: 22225906
PLoS One. 2011;6(8):e23067
pubmed: 21901120
J Cell Sci. 2001 Aug;114(Pt 16):2989-3000
pubmed: 11686302
Cell Death Dis. 2018 Feb 15;9(3):257
pubmed: 29449533
Cell Death Differ. 2002 Sep;9(9):873-80
pubmed: 12181738
Cancer Res. 2008 Jul 15;68(14):5849-58
pubmed: 18632639
Breast Cancer Res. 2013 Feb 25;15(1):202
pubmed: 23673317
Biomaterials. 2009 Oct;30(29):5486-96
pubmed: 19640581
Amino Acids. 2013 Jan;44(1):179-87
pubmed: 22194042
Circ Res. 2005 Jan 7;96(1):119-26
pubmed: 15550691
J Biol Chem. 2010 Dec 17;285(51):40212-29
pubmed: 20929862
J Biol Chem. 1990 Nov 5;265(31):18952-60
pubmed: 2172240
Amino Acids. 2013 Jan;44(1):261-9
pubmed: 21984378
J Med Chem. 2014 Nov 13;57(21):9042-64
pubmed: 25333388
Circ Res. 2010 Jul 9;107(1):117-25
pubmed: 20489165
Science. 1994 Jun 10;264(5165):1593-6
pubmed: 7911253
Int Rev Cell Mol Biol. 2012;294:1-97
pubmed: 22364871
Amino Acids. 2013 Jan;44(1):119-27
pubmed: 22160259
Amino Acids. 2012 Feb;42(2-3):939-49
pubmed: 21818567
Hypertension. 1999 Jan;33(1):116-23
pubmed: 9931091
Antioxid Redox Signal. 2017 Jan 20;26(3):137-149
pubmed: 26906466
Tissue Eng. 2005 Jan-Feb;11(1-2):267-76
pubmed: 15738681
Mol Cancer Ther. 2011 Apr;10(4):626-36
pubmed: 21330459
J Biol Chem. 2003 Oct 24;278(43):42604-14
pubmed: 12732629
Exp Cell Res. 2011 Feb 1;317(3):367-81
pubmed: 21036168
Nat Rev Mol Cell Biol. 2003 Feb;4(2):140-56
pubmed: 12563291
Oncogene. 2017 May 25;36(21):2981-2990
pubmed: 27941875
J Neurochem. 2009 May;109 Suppl 1:160-6
pubmed: 19393023
Gen Pharmacol. 1988;19(1):61-5
pubmed: 2894333
PLoS One. 2014 Feb 20;9(2):e89285
pubmed: 24586660
Acta Cir Bras. 2018 Nov;33(11):991-999
pubmed: 30517326
J Med Chem. 2017 Sep 28;60(18):7910-7927
pubmed: 28858494
J Am Soc Nephrol. 2007 Dec;18(12):3078-88
pubmed: 18003782
Am J Physiol Heart Circ Physiol. 2019 Jul 1;317(1):H49-H59
pubmed: 31002285
Physiol Rev. 2017 Oct 1;97(4):1555-1617
pubmed: 28954852
J Biol Chem. 2008 Jul 25;283(30):20937-47
pubmed: 18499669
Curr Pharm Des. 2008;14(3):278-88
pubmed: 18220838
J Alzheimers Dis. 2014;42 Suppl 3:S289-303
pubmed: 24685636
J Cell Biol. 2000 Feb 21;148(4):825-38
pubmed: 10684262
Trends Pharmacol Sci. 2015 Jan;36(1):32-40
pubmed: 25500711
Mol Cancer Ther. 2019 Jun;18(6):1057-1068
pubmed: 31015308