RGD Reference Report - Upregulation of hypoxia-inducible factors in normal and psoriatic skin. - Rat Genome Database

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Upregulation of hypoxia-inducible factors in normal and psoriatic skin.

Authors: Rosenberger, C  Solovan, C  Rosenberger, AD  Jinping, L  Treudler, R  Frei, U  Eckardt, KU  Brown, LF 
Citation: Rosenberger C, etal., J Invest Dermatol. 2007 Oct;127(10):2445-52. Epub 2007 May 10.
RGD ID: 10395383
Pubmed: PMID:17495954   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.jid.5700874   (Journal Full-text)

Angiogenesis induced by vascular endothelial growth factor (VEGF) plays an important role in psoriasis. Hypoxic adaptation is conferred through hypoxia-inducible transcription factors (HIFs). VEGF and its receptor Flt-1 are HIF target genes. Growth factors and inflammatory cytokines activate the phosphoinositol-3 kinase pathway, and via activated protein kinase B (phospho-Akt) augment HIF activity. Here, we demonstrate that the major oxygen-dependent HIF isoforms are strongly upregulated in psoriatic skin: HIF-1alpha mainly in the epidermis, in an expression pattern similar to VEGF mRNA; HIF-2alpha in both the epidermis and in capillary endothelial cells of the dermis. In contrast, normal human skin shows low expression of HIF-alpha proteins, with the exception of hair follicles, and glands, which strongly express HIF-1alpha. In normal human skin, phospho-Akt appeared in the basal epidermal layer, in hair follicles, and in dermal glands. In contrast, in psoriasis, phospho-Akt expression was low in the epidermis, but markedly enhanced in the dermal capillaries and in surrounding interstitial/inflammatory cells. Our data suggest that hypoxia initiates a potentially self-perpetuating cycle involving HIF, VEGF, and Akt activation, which could drive physiologic growth of hair follicles and skin glands. Furthermore, such a cycle may exist in psoriasis in dermal capillaries and contribute to disease progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
psoriasis  IEP 10395383; 10395383 RGD 
psoriasis  ISOEPAS1 (Homo sapiens)10395383; 10395383 RGD 
psoriasis  ISOHIF1A (Homo sapiens)10395383; 10395383 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Epas1  (endothelial PAS domain protein 1)
Hif1a  (hypoxia inducible factor 1 subunit alpha)

Genes (Mus musculus)
Epas1  (endothelial PAS domain protein 1)
Hif1a  (hypoxia inducible factor 1, alpha subunit)

Genes (Homo sapiens)
EPAS1  (endothelial PAS domain protein 1)
HIF1A  (hypoxia inducible factor 1 subunit alpha)


Additional Information