Abstract
Cardiovascular diseases remain the leading cause of global mortality. Cellular senescence has recently been implicated in the pathogenesis of various cardiovascular diseases. Our group has previously shown that the matricellular protein CCN5 is a potent anti-fibrotic molecule capable of inhibiting and reversing cardiac fibrosis. In this study, we investigated whether CCN5 can modulate cellular senescence in the heart utilizing three readouts: western blotting for p53 and p21, staining for senescence-associated β-galactosidase, and microscopic analysis of γH2AX-foci. CCN5 effectively inhibited doxorubicin-induced cellular senescence in both H9c2 cardiac myoblasts and fibroblasts. In addition, CCN5 suppressed cellular senescence in H9c2 cardiac myoblasts induced by the senescence-associated secretory phenotype factors secreted from cardiac fibroblast, and vice versa. CCN5 also restored the apoptotic response of senescent cells. Finally, CCN5 attenuated myocardial infarction-induced cellular senescence in mice. Collectively, our findings provide novel insights into the potential role of CCN5 in the development of anti-senescence therapies.
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All relevant data are within this paper and its Supporting Information files. The datasets used or analyzed during this study are available from the corresponding authors upon reasonable request.
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Acknowledgements
We thank Dr. YS. Oh (Central Research Facility of Gwangju Institute of Science and Technology) for technical assistance of the confocal microscopy. Figures 1 A, 2 A, 3 A, 4 A, 5 A and 5D were created with BioRender.com. (https://www.biorender.com, https://BioRender.com/w1 × 0kdx). During the preparation of this manuscript, the authors used ChatGPT (version 5.0) to assist with proofreading and improving the readability of the manuscript. All content was reviewed and edited by the authors, who take full responsibility for the final version of the publication.
Funding
This study was supported by funding from the Korea–US Collaborative Research Fund (RS-2024-00466906), the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM5362521) and National Research Council of Science & Technology (NST) grant by the Korea government (MSIT) (GTL24022-000).
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Conceptualization, S.P.J. and W.J.P.; methodology, Y.J.J. and M.Y.L.; validation, S.B.K., Y.J.J. and M.Y.L.; formal analysis, Y.J.J.; investigation, Y.J.J.; data curation, S.B.K. and S.P.J.; writing—original draft preparation, Y.J.J.; writing—review and editing, Y.J.J., S.P.J. and W.J.P.; supervision, S.P.J. and W.J.P.; Resources, T.H.K. and D.T.J.; project administration, W.J.P.; funding acquisition, W.J.P.
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Jo, Y., Lee, M., Kim, S.B. et al. The matricellular protein CCN5 (WISP2) inhibits cellular senescence in cardiac myoblasts and fibroblasts. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40206-1
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DOI: https://doi.org/10.1038/s41598-026-40206-1
