Embryonic NIPP1 Depletion in Keratinocytes Triggers a Cell Cycle Arrest and Premature Senescence in Adult Mice
(2024) The Journal of Investigative Dermatology — Vol. 144, n° 10, p. 2162-2175 (2024)
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- Authors
Jonkhout, Marloes C.M. 
Vanhessche, Tijs Ferreira, Mónica Verbinnen, Iris Bollen, Mathieu
- Abstract
- NIPP1 is a ubiquitously expressed regulatory subunit of PP1. Its embryonic deletion in keratinocytes causes chronic sterile skin inflammation, epidermal hyperproliferation, and resistance to mutagens in adult mice. To explore the primary effects of NIPP1 deletion, we first examined hair cycle progression of NIPP1 skin knockouts (SKOs). The entry of the first hair cycle in the SKOs was delayed owing to prolonged quiescence of hair follicle stem cells. In contrast, the entry of the second hair cycle in the SKOs was advanced as a result of precocious activation of hair follicle stem cells. The epidermis of SKOs progressively accumulated senescent cells, and this cell-fate switch was accelerated by DNA damage. Primary keratinocytes from SKO neonates and human NIPP1-depleted HaCaT keratinocytes failed to proliferate and showed an increase in the expression of cell cycle inhibitors (p21, p16/Ink4a, and/or p19/Arf) and senescence-associated-secretory-phenotype factors as well as in DNA damage (γH2AX and 53BP1). Our data demonstrate that the primary effect of NIPP1 deletion in keratinocytes is a cell cycle arrest and premature senescence that gradually progresse to chronic senescence and likely contribute to the decreased sensitivity of SKOs to mutagens.
- Affiliations
KUL
Citations
Jonkhout, M. C. M., Vanhessche, T., Ferreira, M., Verbinnen, I., Withof, F., Van der Hoeven, G., Szekér, K., Azhir, Z., Lien, W.-H., Van Eynde, A., & Bollen, M. (2024). Embryonic NIPP1 Depletion in Keratinocytes Triggers a Cell Cycle Arrest and Premature Senescence in Adult Mice. The Journal of Investigative Dermatology, 144(10), 2162-2175. https://doi.org/10.1016/j.jid.2024.02.009 (Original work published 2024)