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PMID: 8064230 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.

The Journal of experimental medicine ·Vol. 180 ·No. 3 ·1994-09-01 ·Pages 1141-6

Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF

Abstract

Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.

MeSH Terms
Base Sequence Cells, Cultured Endothelial Growth Factors/biosynthesis,genetics Humans Lymphokines/biosynthesis,genetics Molecular Sequence Data Psoriasis/metabolism RNA, Messenger/analysis Receptor Protein-Tyrosine Kinases/biosynthesis,genetics Receptors, Growth Factor/biosynthesis,genetics Receptors, Vascular Endothelial Growth Factor Transforming Growth Factor alpha/pharmacology Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Endothelial Growth Factors Lymphokines RNA, Messenger Receptors, Growth Factor Transforming Growth Factor alpha Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Receptor Protein-Tyrosine Kinases Receptors, Vascular Endothelial Growth Factor
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Detmar M
Department of Pathology, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Brown L F
Claffey K P
Yeo K T
Kocher O
Jackman R W
Berse B
Dvorak H F
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.180.3.1141
Published
1994-09-01
Pages
1141-6
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191647
Subset
IM
Grants
NCI NIH HHS · CA-50453 · United States
NCI NIH HHS · CA-58845 · United States
External Links
PubMed source DOI: 10.1084/jem.180.3.1141 PMC Full Text View journal details
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