TY - JOUR
T1 - HDAC2 and 7 down-regulation induces senescence in dermal fibroblasts
AU - Warnon, Céline
AU - Bouhjar, Karim
AU - Ninane, Noëlle
AU - Verhoyen, Mathilde
AU - Fattaccioli, Antoine
AU - Fransolet, Maude
AU - Lambert de Rouvroit, Catherine
AU - Poumay, Yves
AU - Piel, Géraldine
AU - Mottet, Denis
AU - Debacq-Chainiaux, Florence
N1 - Funding Information:
The authors thank Natacha Zanin for her careful checking of the manuscript, and Emmanuel Di Valentin and the Viral Vectors Platform (Giga, Liège, Belgium) for their technical help in viral vectors design and production. FDC and DM are research associates at FRS-FNRS (National Funds for Scientific Research, Belgium).
Publisher Copyright:
© 2021. Warnon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/7/31
Y1 - 2021/7/31
N2 - Originally simply reported to be in a stable and irreversible growth arrest in vitro, senescent cells are now clearly associated with normal and pathological ageing in vivo. They are characterized by several biomarkers and changes in gene expression that may depend on epigenetic factors, such as histone acetylation, involving a balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we investigate the expression and the role of HDACs on the senescent phenotype of dermal fibroblasts. We report that during replicative senescence, most canonical HDACs are less expressed. Moreover, treatment with SAHA, a histone deacetylase inhibitor (HDACi) also known as Vorinostat, or the specific downregulation of HDAC2 or HDAC7 by siRNA, induces the appearance of senescence biomarkers of dermal fibroblasts. Conversely, the ectopic re-expression of HDAC7 by lentiviral transduction in pre-senescent dermal fibroblasts extends their proliferative lifespan. These results demonstrate that HDACs expression can modulate the senescent phenotype, highlighting their pharmaceutical interest in the context of healthy ageing.
AB - Originally simply reported to be in a stable and irreversible growth arrest in vitro, senescent cells are now clearly associated with normal and pathological ageing in vivo. They are characterized by several biomarkers and changes in gene expression that may depend on epigenetic factors, such as histone acetylation, involving a balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we investigate the expression and the role of HDACs on the senescent phenotype of dermal fibroblasts. We report that during replicative senescence, most canonical HDACs are less expressed. Moreover, treatment with SAHA, a histone deacetylase inhibitor (HDACi) also known as Vorinostat, or the specific downregulation of HDAC2 or HDAC7 by siRNA, induces the appearance of senescence biomarkers of dermal fibroblasts. Conversely, the ectopic re-expression of HDAC7 by lentiviral transduction in pre-senescent dermal fibroblasts extends their proliferative lifespan. These results demonstrate that HDACs expression can modulate the senescent phenotype, highlighting their pharmaceutical interest in the context of healthy ageing.
KW - fibroblasts
KW - histone deacetylases
KW - SAHA
KW - SASP
KW - senescence
UR - http://www.scopus.com/inward/record.url?scp=85112338137&partnerID=8YFLogxK
U2 - 10.18632/aging.203304
DO - 10.18632/aging.203304
M3 - Article
C2 - 34253688
SN - 1945-4589
VL - 13
SP - 17978
EP - 18005
JO - Aging
JF - Aging
IS - 14
ER -