Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Replicative Senescence in Vascular Smooth Muscle Cells: PURPL and NEAT1 Long Non-Coding RNAs as New Senescence-Associated Biomarkers

Clara Rossi
ORCID logo ,
Marco Venturin
ORCID logo ,
Jakub Gubala
ORCID logo ,
Angelisa Frasca
ORCID logo ,
Alberto Corsini
,
Cristina Battaglia
ORCID logo ,
Stefano Bellosta
* ORCID logo
Version 1 : Received: 23 July 2023 / Approved: 24 July 2023 / Online: 24 July 2023 (10:02:09 CEST)

A peer-reviewed article of this Preprint also exists.

Rossi, C.; Venturin, M.; Gubala, J.; Frasca, A.; Corsini, A.; Battaglia, C.; Bellosta, S. PURPL and NEAT1 Long Non-Coding RNAs Are Modulated in Vascular Smooth Muscle Cell Replicative Senescence. Biomedicines 2023, 11, 3228. https://doi.org/10.3390/biomedicines11123228 Rossi, C.; Venturin, M.; Gubala, J.; Frasca, A.; Corsini, A.; Battaglia, C.; Bellosta, S. PURPL and NEAT1 Long Non-Coding RNAs Are Modulated in Vascular Smooth Muscle Cell Replicative Senescence. Biomedicines 2023, 11, 3228. https://doi.org/10.3390/biomedicines11123228

Abstract

Cellular senescence is characterized by permanent proliferation and migration arrest, senescence-associated secretory phenotype (SASP), and oxidative stress. Senescent vascular smooth muscle cells (VSMCs) contribute to cardiovascular diseases and atherosclerotic plaque instability. To establish and characterize a model of replicative senescence (RS), human aortic VSMCs were serially passaged to represent different stages of RS such as young proliferating cells and old/senescent non-proliferating cells. More than 50% of old cells stained positive for the senescence-associated β-galactosidase compared to 20% of young cells. Old cells have a slower proliferation rate, a migratory activity reduced by 50%, but increased levels of TP53 and of cell cycle inhibitors p21/p16 expression, and accumulate in the G1 phase. Old cells showed a flattened appearance and enlarged and regular nuclei, and downregulation of the expression of LMNB1 and HMGB1. Old cells showed also an increased expression of SASP molecules (IL1β, IL6, IL8, and MMP3). Moreover, among a set of 12 manually selected long non-coding RNAs (lncRNAs), we detected significant upregulation of PURPL and NEAT1. We observed also increased levels of RRAD mRNA. The detection of novel molecular markers of senescence, such as RRAD, PURPL, and NEAT1, could be helpful for future studies on potential anti-aging factors.

Keywords

aging; biomarkers; lncRNA; NEAT1; PURPL; RRAD; senescence; smooth muscle cells

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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