| First Author | Yamaguchi Y | Year | 2015 |
| Journal | J Invest Dermatol | Volume | 135 |
| Issue | 11 | Pages | 2764-2774 |
| PubMed ID | 26134945 | Mgi Jnum | J:226340 |
| Mgi Id | MGI:5697109 | Doi | 10.1038/jid.2015.249 |
| Citation | Yamaguchi Y, et al. (2015) Decreased Expression of Caveolin-1 Contributes to the Pathogenesis of Psoriasiform Dermatitis in Mice. J Invest Dermatol 135(11):2764-74 |
| abstractText | Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal keratinocyte development, in which T helper type 17 cells and signal transducer and activator of transcription 3 (STAT3) activation have pivotal roles. Moreover, caveolin-1 (CAV-1) has been implicated in the regulation of signal transduction, and aberrant CAV-1 expression is involved in a variety of diseases. However, whether CAV-1 is involved in psoriasis is unknown. Here we examined CAV-1 expression in the psoriatic epidermis and investigated its role in the pathogenesis of psoriasis. CAV-1 was markedly reduced in lesional epidermis of psoriasis patients. CAV1 silencing in keratinocytes in vitro revealed significant activation of STAT3, leading to increased expression of keratin 16 and several cytokine/chemokines, such as IL-6, C-X-C chemokine ligand 8 (CXCL8), CXCL9, and C-C chemokine ligand 20. In addition, psoriasis-related cytokines, including tumor necrosis factor-alpha (TNF-alpha), decreased CAV-1 expression in keratinocytes. Finally, administration of CAV-1 scaffolding domain peptide in a murine model of psoriasis-like skin inflammation induced by imiquimod improved the skin phenotype and reduced epidermal thickness and infiltrating cell counts. Furthermore, expression of TNF-alpha, IL-17A, and IL-23 was significantly suppressed by this treatment. Collectively, our study indicated that CAV-1 participates in the pathogenesis of psoriasis by regulating the STAT3 pathway and cytokine networks. |
