VGLL3 activates inflammatory responses by inducing interleukin-1α secretion.
FASEB J
; 35(11): e21996, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34679187
ABSTRACT
Vestigial-like family member 3 (VGLL3), a member of the vestigial-like family, is a cofactor of the TEA-domain-containing transcription factor (TEAD). Although elevation in VGLL3 expression is associated with inflammatory diseases, such as inflammatory sarcomas and autoimmune diseases, the molecular mechanisms underlying VGLL3-mediated inflammation remain largely unknown. In this study, we analyzed the relationship between elevated VGLL3 expression and the levels of NF-κB, a transcription factor that plays a pivotal role in inflammation. NF-κB was found to be activated in a cell line stably expressing VGLL3. Mechanistically, VGLL3 was shown to promote the expression and secretion of the potent NF-κB-activating cytokine interleukin (IL)-1α, probably through its association with TEADs. As VGLL3 is a target of transforming growth factor ß (TGF-ß) signaling, we analyzed IL-1α induction upon TGF-ß stimulation. TGF-ß stimulation was observed to induce IL-1α secretion and NF-κB activation, and VGLL3 was associated with this phenomenon. The TGF-ß transcription factors Smad3 and Smad4 were shown to be necessary for inducing VGLL3 and IL-1α expression. Lastly, we found that VGLL3-dependent IL-1α secretion is involved in constitutive NF-κB activation in highly malignant breast cancer cells. Collectively, the findings suggested that VGLL3 expression and TGF-ß stimulation activate the inflammatory response by inducing IL-1α secretion.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
FN-kappa B
/
Factor de Crecimiento Transformador beta
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Interleucina-1alfa
/
Inflamación
Límite:
Humans
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón