Niklander, S., Bandaru, D., Lambert, D.W. et al. (1 more author) (2020) ROCK inhibition modulates the senescence‐associated secretory phenotype (SASP) in oral keratinocytes. FEBS Open Bio, 10 (12). pp. 2740-2749. ISSN 2211-5463
Abstract
Senescent cells accumulate in different organs and develop a senescence‐associated secretory phenotype (SASP), associated with the development of age‐related pathologies. The constitution of the SASP varies among cell types and with the method of senescence induction; nevertheless, there is substantial overlap among SASPs, especially the presence of pro‐inflammatory cytokines such as IL‐1β, IL‐1α, IL‐6 and IL‐8. These cytokines are highly conserved among SASPs and are implicated in the development of several cancers. Here, we report that ROCK inhibition by Y‐27632 reduces levels of IL‐1α, IL‐1β, IL‐6 and IL‐8 secreted by senescent normal and dysplastic oral keratinocytes without affecting the permanent cell growth arrest. The data indicate some inflammatory genes downregulated by Y‐27632 remain downregulated even after repeated passage in the absence of Y‐27632. We propose ROCK kinase inhibition as a novel alternative to current strategies to modulate the inflammatory components of the SASP, without compromising the permanent cell growth arrest. This observation potentially has wide clinical applications, given the involvement of senescence in cancer and a wide range of age‐related disease. It also suggests care should be exercised when using Y‐27632 to facilitate cell expansion of primary cells, as its effects on gene expression are not entirely reversible.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Rho‐kinase; ROCK inhibitors; Y‐27632; senescence; SASP |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 04 Nov 2020 11:51 |
Last Modified: | 09 Feb 2022 07:57 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/2211-5463.13012 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167365 |