Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: Implications for the pathogenesis of psoriasis

Peter M. Elias, Jack Arbiser, Barbara E. Brown, Heidemarie Rossiter, Mao Qiang Man, Francesca Cerimele, Debra Crumrine, Roshan Gunathilake, Eung Ho Choi, Yoshikazu Uchida, Erwin Tschachler, Kenneth R. Feingold

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf -/- mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

Original languageEnglish
Pages (from-to)689-699
Number of pages11
JournalAmerican Journal of Pathology
Volume173
Issue number3
DOIs
Publication statusPublished - 2008 Jan 1

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Psoriasis
Vascular Endothelial Growth Factor A
Hyperplasia
Permeability
Homeostasis
Skin
Hairless Mouse
Wounds and Injuries
Capillary Permeability
Atopic Dermatitis
Skin Diseases
Intercellular Signaling Peptides and Proteins
Up-Regulation
Maintenance
Cytokines
Inflammation
Messenger RNA
Membranes
Proteins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Elias, Peter M. ; Arbiser, Jack ; Brown, Barbara E. ; Rossiter, Heidemarie ; Man, Mao Qiang ; Cerimele, Francesca ; Crumrine, Debra ; Gunathilake, Roshan ; Choi, Eung Ho ; Uchida, Yoshikazu ; Tschachler, Erwin ; Feingold, Kenneth R. / Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia : Implications for the pathogenesis of psoriasis. In: American Journal of Pathology. 2008 ; Vol. 173, No. 3. pp. 689-699.
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Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia : Implications for the pathogenesis of psoriasis. / Elias, Peter M.; Arbiser, Jack; Brown, Barbara E.; Rossiter, Heidemarie; Man, Mao Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R.

In: American Journal of Pathology, Vol. 173, No. 3, 01.01.2008, p. 689-699.

Research output: Contribution to journalArticle

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AU - Rossiter, Heidemarie

AU - Man, Mao Qiang

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AU - Choi, Eung Ho

AU - Uchida, Yoshikazu

AU - Tschachler, Erwin

AU - Feingold, Kenneth R.

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