TY - JOUR
T1 - The Protective Role of pVHL in Imiquimod-Induced Psoriasis-like Skin Inflammation
AU - Martínez-Torres, Isaí
AU - Tepale-Segura, Araceli
AU - Castro-Escamilla, Octavio
AU - Cancino-Diaz, Juan Carlos
AU - Rodríguez-Martínez, Sandra
AU - Perez-Tapia, Sonia Mayra
AU - Bonifaz, Laura C.
AU - Cancino-Diaz, Mario Eugenio
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Psoriasis is a chronic inflammatory disease distinguished by an excessive proliferation and abnormal differentiation of keratinocytes. Immune cells, such as T lymphocytes and neutro-phils, and inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and interleukin 17 (IL-17), are essential for maintaining psoriatic lesions. Additionally, a hypoxic milieu present in the skin promotes the expression of transcriptional factor hypoxia-inducible factor-1 alpha (HIF-1α). This protein regulates the expression of angiogenic and glycolytic factors, such as vascular endothelial grown factor and lactate dehydrogenase (LDH), both relevant in chronic inflammation. The von Hippel–Lindau protein (pVHL) is a negative regulator of HIF-1α. Previously, we found that pVHL was almost absent in the lesions of psoriasis patients; therefore, we investigated the impact of rescue pVHL expression in lesional skin. We used the imiquimod-induced psoriasis-like mouse model as an adenoviral vector that allowed us to express pVHL in the skin. Our data show that, in lesional skin, pVHL expression was reduced, whereas HIF-1α was increased. Remarkably, the retrieval of pVHL prevented psoriatic lesions, diminishing erythema, scale, and epidermal and vascular thickness. Furthermore, pVHL expression was capable of reducing HIF-1α, LDH, TNF-α and immune cell infiltration (mainly IL-17+ neutrophils). In conclusion, our results demonstrate that pVHL has a protective role to play in the pathophysiology of psoriasis.
AB - Psoriasis is a chronic inflammatory disease distinguished by an excessive proliferation and abnormal differentiation of keratinocytes. Immune cells, such as T lymphocytes and neutro-phils, and inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and interleukin 17 (IL-17), are essential for maintaining psoriatic lesions. Additionally, a hypoxic milieu present in the skin promotes the expression of transcriptional factor hypoxia-inducible factor-1 alpha (HIF-1α). This protein regulates the expression of angiogenic and glycolytic factors, such as vascular endothelial grown factor and lactate dehydrogenase (LDH), both relevant in chronic inflammation. The von Hippel–Lindau protein (pVHL) is a negative regulator of HIF-1α. Previously, we found that pVHL was almost absent in the lesions of psoriasis patients; therefore, we investigated the impact of rescue pVHL expression in lesional skin. We used the imiquimod-induced psoriasis-like mouse model as an adenoviral vector that allowed us to express pVHL in the skin. Our data show that, in lesional skin, pVHL expression was reduced, whereas HIF-1α was increased. Remarkably, the retrieval of pVHL prevented psoriatic lesions, diminishing erythema, scale, and epidermal and vascular thickness. Furthermore, pVHL expression was capable of reducing HIF-1α, LDH, TNF-α and immune cell infiltration (mainly IL-17+ neutrophils). In conclusion, our results demonstrate that pVHL has a protective role to play in the pathophysiology of psoriasis.
KW - IL-17
KW - angiogenesis
KW - hypoxia-inducible factor-1α (HIF-1α)
KW - neutrophils
KW - psoriasis
KW - von Hippel-Lindau protein (pVHL)
UR - http://www.scopus.com/inward/record.url?scp=85129355869&partnerID=8YFLogxK
U2 - 10.3390/ijms23095226
DO - 10.3390/ijms23095226
M3 - Artículo
C2 - 35563616
AN - SCOPUS:85129355869
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 9
M1 - 5226
ER -