TY - JOUR
T1 - Under-expression of VHL and over-expression of HDAC-1, HIF-1α, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis
AU - Tovar-Castillo, Laura E.
AU - Cancino-Díaz, Juan C.
AU - García-Vázquez, Francisco
AU - Cancino-Gómez, Francisco G.
AU - León-Dorantes, Gladys
AU - Blancas-González, Fernando
AU - Jiménez-Zamudio, Luis
AU - García-Latorre, Ethel
AU - Cancino-Díaz, Mario E.
PY - 2007/3
Y1 - 2007/3
N2 - Background: A feature of psoriasis is the rapid proliferation of keratinocytes, during which apoptosis is blocked and angiogenesis starts. It is known that tumor hypoxic cells produce histone deacetylase-1 (HDAC-1), which up-regulates hypoxia-inducible factor-1α (HIF-1α) and down-regulates von Hippel-Lindau (VHL) protein by up-regulating vascular endothelial growth factor (VEGF) expression. It has been reported recently that the porcine peptide PR39 (homologous to human LL-37) has angiogenic and antiapoptotic activity. Thus, LL-37, induced by insulin-like growth factor-1 (IGF-1), could help in the production of VEGF. PR39 also induces the expression of inhibitor of apoptosis protein-2 (IAP-2), which blocks apoptosis. The purpose of this work was to analyze whether these genes and their proteins are expressed in psoriatic biopsies. Methods: Using semiquantitative revers e transcriptase-polymerase chain reaction (RT-PCR) messenger RNA (mRNA) expression and immunohistochemical staining, we studied VHL, IAP-2, and related genes in skin biopsies from psoriatic patients and healthy subjects. Results: An over-expression of the mRNA for HDAC-1, HIF-1α, LL-37, and IGF-1 in psoriatic skin, in comparison with skin from healthy subjects, was found. The antiangiogenic VHL mRNA and protein were under-expressed in psoriatic skin and highly expressed in healthy skin. The antiapoptotic IAP-2 was over-expressed in dermal endothelial cells from psoriatic skin. The pro-apoptotic Bax, Fas, and FasL mRNAs were expressed. Conclusions: These findings suggest that there could be an a ssociation of HDAC-1, HIF-1α, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis.
AB - Background: A feature of psoriasis is the rapid proliferation of keratinocytes, during which apoptosis is blocked and angiogenesis starts. It is known that tumor hypoxic cells produce histone deacetylase-1 (HDAC-1), which up-regulates hypoxia-inducible factor-1α (HIF-1α) and down-regulates von Hippel-Lindau (VHL) protein by up-regulating vascular endothelial growth factor (VEGF) expression. It has been reported recently that the porcine peptide PR39 (homologous to human LL-37) has angiogenic and antiapoptotic activity. Thus, LL-37, induced by insulin-like growth factor-1 (IGF-1), could help in the production of VEGF. PR39 also induces the expression of inhibitor of apoptosis protein-2 (IAP-2), which blocks apoptosis. The purpose of this work was to analyze whether these genes and their proteins are expressed in psoriatic biopsies. Methods: Using semiquantitative revers e transcriptase-polymerase chain reaction (RT-PCR) messenger RNA (mRNA) expression and immunohistochemical staining, we studied VHL, IAP-2, and related genes in skin biopsies from psoriatic patients and healthy subjects. Results: An over-expression of the mRNA for HDAC-1, HIF-1α, LL-37, and IGF-1 in psoriatic skin, in comparison with skin from healthy subjects, was found. The antiangiogenic VHL mRNA and protein were under-expressed in psoriatic skin and highly expressed in healthy skin. The antiapoptotic IAP-2 was over-expressed in dermal endothelial cells from psoriatic skin. The pro-apoptotic Bax, Fas, and FasL mRNAs were expressed. Conclusions: These findings suggest that there could be an a ssociation of HDAC-1, HIF-1α, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis.
UR - http://www.scopus.com/inward/record.url?scp=33847793536&partnerID=8YFLogxK
U2 - 10.1111/j.1365-4632.2006.02962.x
DO - 10.1111/j.1365-4632.2006.02962.x
M3 - Artículo
SN - 0011-9059
VL - 46
SP - 239
EP - 246
JO - International Journal of Dermatology
JF - International Journal of Dermatology
IS - 3
ER -