TY - JOUR
T1 - Aging-regulated TUG1 is dispensable for endothelial cell function
AU - Gimbel, Anna Theresa
AU - Koziarek, Susanne
AU - Theodorou, Kosta
AU - Schulz, Jana Felicitas
AU - Stanicek, Laura
AU - Kremer, Veerle
AU - Ali, Tamer
AU - Günther, Stefan
AU - Kumar, Sandeep
AU - Jo, Hanjoong
AU - Hübner, Norbert
AU - Maegdefessel, Lars
AU - Dimmeler, Stefanie
AU - van Heesch, Sebastiaan
AU - Boon, Reinier A.
N1 - Publisher Copyright: © 2022 Gimbel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/9/29
Y1 - 2022/9/29
N2 - The evolutionary conserved Taurine Upregulated Gene 1 (TUG1) is a ubiquitously expressed gene that is one of the highest expressed genes in human and rodent endothelial cells (ECs). We here show that TUG1 expression decreases significantly in aging mouse carotid artery ECs and human ECs in vitro, indicating a potential role in the aging endothelial vasculature system. We therefore investigated if, and how, TUG1 might function in aging ECs, but despite extensive phenotyping found no alterations in basal EC proliferation, apoptosis, barrier function, migration, mitochondrial function, or monocyte adhesion upon TUG1 silencing in vitro. TUG1 knockdown did slightly and significantly decrease cumulative sprout length upon vascular endothelial growth factor A stimulation in human umbilical vein endothelial cells (HUVECs), though TUG1-silenced HUVECs displayed no transcriptomewide mRNA expression changes explaining this effect. Further, ectopic expression of the highly conserved and recently discovered 153 amino acid protein translated from certain TUG1 transcript isoforms did not alter angiogenic sprouting in vitro. Our data show that, despite a high expression and strong evolutionary conservation of both the TUG1 locus and the protein sequence it encodes, TUG1 does not seem to play a major role in basic endothelial cell function.
AB - The evolutionary conserved Taurine Upregulated Gene 1 (TUG1) is a ubiquitously expressed gene that is one of the highest expressed genes in human and rodent endothelial cells (ECs). We here show that TUG1 expression decreases significantly in aging mouse carotid artery ECs and human ECs in vitro, indicating a potential role in the aging endothelial vasculature system. We therefore investigated if, and how, TUG1 might function in aging ECs, but despite extensive phenotyping found no alterations in basal EC proliferation, apoptosis, barrier function, migration, mitochondrial function, or monocyte adhesion upon TUG1 silencing in vitro. TUG1 knockdown did slightly and significantly decrease cumulative sprout length upon vascular endothelial growth factor A stimulation in human umbilical vein endothelial cells (HUVECs), though TUG1-silenced HUVECs displayed no transcriptomewide mRNA expression changes explaining this effect. Further, ectopic expression of the highly conserved and recently discovered 153 amino acid protein translated from certain TUG1 transcript isoforms did not alter angiogenic sprouting in vitro. Our data show that, despite a high expression and strong evolutionary conservation of both the TUG1 locus and the protein sequence it encodes, TUG1 does not seem to play a major role in basic endothelial cell function.
UR - http://www.scopus.com/inward/record.url?scp=85138983398&partnerID=8YFLogxK
U2 - https://doi.org/10.1371/journal.pone.0265160
DO - https://doi.org/10.1371/journal.pone.0265160
M3 - Article
C2 - 36173935
SN - 1932-6203
VL - 17
JO - PLOS ONE
JF - PLOS ONE
M1 - e0265160
ER -