NF-κB/IKK Activation by Small Extracellular Vesicles Within the SASP

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NF-κB/IKK Activation by Small Extracellular Vesicles Within the SASPFecha
2021-06-29Cita bibliográfica
Fafián-Labora JA, O'Logjlen A. NF-κB/IKK activation by small extracellular vesicles within the SASP. Aging Cell. 2021;20(7):e13426
Resumen
[Abstract] Cellular senescence plays an important role in different biological and pathological conditions. Senescent cells communicate with their microenvironment through a plethora of soluble factors, metalloproteases and extracellular vesicles (EV). Although much is known about the role that soluble factors play in senescence, the downstream signalling pathways activated by EV in senescence is unknown. To address this, we performed a small molecule inhibitor screen and have identified the IκB kinases IKKε, IKKα and IKKβ as essential for senescence mediated by EV (evSASP). By using pharmacological inhibitors of IKKε, IKKα and IKKβ, in addition to CRISPR/Cas9 targeting their respective genes, we find these pathways are important in mediating senescence. In addition, we find that senescence activation is dependent on canonical NF-κB transcription factors where siRNA targeting p65 prevent senescence. Importantly, these IKK pathways are also relevant to ageing as knockout of IKKA, IKKB and IKKE avoid the activation of senescence. Altogether, these findings open a new potential line of investigation in the field of senescence by targeting the negative effects of the evSASP independent of particular EV contents.
Palabras clave
IκB kinase (IKK)
NF-κB
SASP
Ageing
Extracellular vesicles (EV)
Senescence
NF-κB
SASP
Ageing
Extracellular vesicles (EV)
Senescence
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Creative Commons Attribution 4.0 International License (CC-BY 4.0)
ISSN
1474-9718