期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 65, 期 2, 页码 134-140出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2011.11.011
关键词
Psoriasis; Wound healing; Cytokines; STAT; SMAD
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [21390323, 23791246]
- Grants-in-Aid for Scientific Research [23791246, 21390323] Funding Source: KAKEN
Background: Podoplanin (PDPN)/T1 alpha/aggrus/PA2.26 antigen, a transmembranous glycoprotein, is a well-known lymphatic endothelial marker. Recent evidence indicates that PDPN is also expressed in keratinocytes especially of sebaceous glands. Objective: To verify expression-pattern and the regulatory mechanism of PDPN in human epidermal keratinocytes. Methods: PDPN-expression pattern was analyzed in normal and psoriatic epidermis by immunostaining. The regulatory mechanism of PDPN-expression of keratinocytes by cytokines was analyzed using specific inhibitors, siRNA, and adenoviral shRNA of signaling pathways. Results: In normal skin. PDPN was expressed on the basal cell layer of sebaceous glands and on the outer root sheath of hair follicles. While no expression was detected in the normal interfollicular epidermis, PDPN was detected in the basal cell layer of wound and hyperproliferative psoriatic epidermis, where the granular layer is lacking. TGF-beta 1 and IFN-gamma independently upregulated PDPN-expression of keratinocytes via TGF-beta receptor-Smad pathway and JAK-STAT pathway, respectively. IL-6 and IL-22 also stimulated PDPN-expression of keratinocytes accompanied by STAT-3 phosphorylation. siRNA of STAT-1, inhibitors of STAT-3 signaling, AG490, STAT-3 inhibitor VI, and si/shRNA of STAT-3 inhibited the PDPN-expression of keratinocytes induced by IFN-gamma, IL-6 and IL-22 but not by TGF-beta 1. Conclusion: These results indicate that TGF-beta 1, IFN-gamma, IL-6, and IL-22 induce PDPN-expression of keratinocytes, which might be significantly involved in the wound healing process as well as in the pathomechanism of hyperproliferative psoriatic epidermis. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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