Under-expression of VHL and over-expression of HDAC-1, HIF-1alpha, LL-37, and IAP-2 in affected skin biopsies of patients with psoriasis.
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-1alpha (HIF-1alpha) 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 reverse 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-1alpha, 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 association of HDAC-1, HIF-1alpha, LL-37, VHL, and IAP-2 with angiogenic and apoptotic mechanisms in psoriasis.
Tovar-Castillo
Laura E
LE
Departamentos de Inmunologia and Microbiologia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Servicio de Dermatología, Hospital General de México, Mexico.
Cancino-Díaz
Juan C
JC
García-Vázquez
Francisco
F
Cancino-Gómez
Francisco G
FG
León-Dorantes
Gladys
G
Blancas-González
Fernando
F
Jiménez-Zamudio
Luis
L
García-Latorre
Ethel
E
Cancino-Díaz
Mario E
ME
D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000096:biosynthesis*; D001706:Biopsy; D054804:Cathelicidins; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000096:biosynthesis*; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000032:analysis / Q000096:biosynthesis*
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; C497446:VHL protein, human