Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon.
Wnt5a is a member of the wingless-type patterning regulators important in pre-natal development. The expression and distribution of Wnt5a and its receptors frizzled (fzd) 3 and fzd 5 in adult human skin have not been comprehensively studied to date.We here show that Wnt5a, fzd3, fzd5, as well as fzd...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2670517?pdf=render |
| _version_ | 1818484106231545856 |
|---|---|
| author | Malgorzata Romanowska Alan Evans David Kellock Susan E Bray Kathleen McLean Susanne Donandt John Foerster |
| author_facet | Malgorzata Romanowska Alan Evans David Kellock Susan E Bray Kathleen McLean Susanne Donandt John Foerster |
| author_sort | Malgorzata Romanowska |
| collection | DOAJ |
| description | Wnt5a is a member of the wingless-type patterning regulators important in pre-natal development. The expression and distribution of Wnt5a and its receptors frizzled (fzd) 3 and fzd 5 in adult human skin have not been comprehensively studied to date.We here show that Wnt5a, fzd3, fzd5, as well as fzd6 are restricted to specific layers in normal epidermis, analogous to their zonal distribution in hair follicles, suggesting a role in adult skin differentiation. In line, Wnt5a and fzd5 are both overexpressed and re-distributed in the epidermis of psoriasis which involves disturbed keratinocyte differentiation. Functionally, Wnt5a lowers the concentration of IFN required to induce target genes, and increases the magnitude of IFN target gene induction, suggesting a molecular mechanism underlying IFN hypersensitivity in psoriasis. Finally, we identify nedd8 and the amyloid precursor APP, previously shown to be upregulated in psoriasis, as targets of synergistic IFNalpha/Wnt5a induction.The present data (i) suggest that Wnt5a regulates epidermal differentiation even in adult skin and (ii) identify synergistic induction of type 1 IFN target genes as a novel mode of Wnt5a action. Targeting Wnt5a in the skin may reduce IFN hypersensitivity and be of therapeutical value. |
| first_indexed | 2024-12-10T15:50:47Z |
| format | Article |
| id | doaj.art-9a01c73222504236bfb4272bcb2e15f1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T15:50:47Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9a01c73222504236bfb4272bcb2e15f12022-12-22T01:42:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0144e535410.1371/journal.pone.0005354Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon.Malgorzata RomanowskaAlan EvansDavid KellockSusan E BrayKathleen McLeanSusanne DonandtJohn FoersterWnt5a is a member of the wingless-type patterning regulators important in pre-natal development. The expression and distribution of Wnt5a and its receptors frizzled (fzd) 3 and fzd 5 in adult human skin have not been comprehensively studied to date.We here show that Wnt5a, fzd3, fzd5, as well as fzd6 are restricted to specific layers in normal epidermis, analogous to their zonal distribution in hair follicles, suggesting a role in adult skin differentiation. In line, Wnt5a and fzd5 are both overexpressed and re-distributed in the epidermis of psoriasis which involves disturbed keratinocyte differentiation. Functionally, Wnt5a lowers the concentration of IFN required to induce target genes, and increases the magnitude of IFN target gene induction, suggesting a molecular mechanism underlying IFN hypersensitivity in psoriasis. Finally, we identify nedd8 and the amyloid precursor APP, previously shown to be upregulated in psoriasis, as targets of synergistic IFNalpha/Wnt5a induction.The present data (i) suggest that Wnt5a regulates epidermal differentiation even in adult skin and (ii) identify synergistic induction of type 1 IFN target genes as a novel mode of Wnt5a action. Targeting Wnt5a in the skin may reduce IFN hypersensitivity and be of therapeutical value.http://europepmc.org/articles/PMC2670517?pdf=render |
| spellingShingle | Malgorzata Romanowska Alan Evans David Kellock Susan E Bray Kathleen McLean Susanne Donandt John Foerster Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon. PLoS ONE |
| title | Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon. |
| title_full | Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon. |
| title_fullStr | Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon. |
| title_full_unstemmed | Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon. |
| title_short | Wnt5a exhibits layer-specific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon. |
| title_sort | wnt5a exhibits layer specific expression in adult skin is upregulated in psoriasis and synergizes with type 1 interferon |
| url | http://europepmc.org/articles/PMC2670517?pdf=render |
| work_keys_str_mv | AT malgorzataromanowska wnt5aexhibitslayerspecificexpressioninadultskinisupregulatedinpsoriasisandsynergizeswithtype1interferon AT alanevans wnt5aexhibitslayerspecificexpressioninadultskinisupregulatedinpsoriasisandsynergizeswithtype1interferon AT davidkellock wnt5aexhibitslayerspecificexpressioninadultskinisupregulatedinpsoriasisandsynergizeswithtype1interferon AT susanebray wnt5aexhibitslayerspecificexpressioninadultskinisupregulatedinpsoriasisandsynergizeswithtype1interferon AT kathleenmclean wnt5aexhibitslayerspecificexpressioninadultskinisupregulatedinpsoriasisandsynergizeswithtype1interferon AT susannedonandt wnt5aexhibitslayerspecificexpressioninadultskinisupregulatedinpsoriasisandsynergizeswithtype1interferon AT johnfoerster wnt5aexhibitslayerspecificexpressioninadultskinisupregulatedinpsoriasisandsynergizeswithtype1interferon |