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NRF2 SIGNALING PATHWAY IN PSORIASIS: FRIEND OR FOE?
Autores:
FRANCISCO JAVIER MARTÍNEZ MORCILLO
,
FRANCISCO JUAN MARTINEZ NAVARRO
,
ANTONIO RAUL CORBALÁN VÉLEZ
, MARÍA TERESA MARTÍNEZ MENCHÓN,
JOSE MESEGUER PEÑALVER
,
DIANA GARCIA MORENO
,
VICTORIANO MULERO MÉNDEZ
,
Grupos de investigación:
[GI/IMIB/C060/2011] Inmunidad, inflamación y cáncer
[GI/IMIB/C003/2011] Cirugía digestiva, endocrina y trasplante de órganos abdominales
[GI/IMIB/C006/2011] INMUNOLOGÍA E INMUNOTOLERANCIA EN TRASPLANTES Y ENFERMEDADES DE BASE INMUNOLÓGICA
Comunicación:
Antecedentes:
Psoriasis is a not contagious skin chronic inflammation disease that affects nearly 2% world population. The etiology is still undetermined, but it is known that allergic, genetic, immunological and environmental causes are all involved. Several studies have demonstrated a strong correlation between oxidative stress and skin inflammation in psoriasis patients. In order to elucidate this relationship, we have investigated the nuclear factor-erythroid 2 related factor 2 (Nrf2), which is a redox sensitivity transcriptional factor involved in the induction of numerous genes encoding ROS-scavenging enzymes through binding to the antioxidant response element (ARE).
Métodos:
We have analyzed transcriptomic data from human psoriasis samples available at the GEO database. Using the unique advantages of the zebrafish embryo for in vivo imaging and cell tracking, we have tested by bath immersion the capability of Nrf2-activating compounds coupled to reduced glutathione (GSH) to diminish neutrophils dispersion in Tnfr2-deficient larvae, as an indicator of skin inflammation severity.
Resultados:
The analysis of human transcriptomic data at GEO database showed activation of the NRF2 signaling pathway in psoriatic skin lesions, which is positively correlated with inflammation markers. Preliminary functional analysis in a zebrafish model of skin inflammation showed that pharmacological activation of the NRF2 pathway fail to significantly ameliorate skin inflammation of Tnfr2-deficient animals, likely as a consequence of exhausted GSH pool.
Conclusiones:
Collectively, these results suggest that pharmacological activation of NRF2 combine with administration of GSH could result in an improved protection against oxidative stress in psoriasis, leading to reduced inflammation and disease severity.
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