| Autor: |
Jernej Kristl, Petra Slanc, Metka Krašna, Aleš Berlec, Matjaž Jeras, Borut Štrukelj |
| Předmět: |
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| Zdroj: |
Pharmaceutical Research; Mar2008, Vol. 25 Issue 3, p521-529, 9p |
| Abstrakt: |
Abstract Purpose Calcipotriol is a potent drug for topical treatment of psoriasis because it manages to inhibit keratinocyte proliferation. In the present study we investigated the effects of calcipotriol on gene expression in human keratinocytes in terms of mechanism of how calcipotriol decreases proliferation. Materials and methods Cell proliferation was analyzed by MTT assay. The differential display approach together with qPCR was used to assess the gene expression after treatment. In addition, Western immunoblotting revealed differences on the protein level. Finally, transfection of the KCs with specific small interfering RNA determined the genes necessary to inhibit proliferation. Results KCs proliferation was decreased in a concentration-dependent manner. Moreover, calcipotriol dowregulated the expression of two proliferation factors: early growth response-1 (EGR1) and polo-like kinase-2 (PLK2). The protein levels of EGR1 and PLK2 were also decreased. Specific siRNA against EGR1 and PLK2 in KCs resulted in marked reduction of EGR1 and PLK2 expression. In both cases, the reduction resolved in the decreased proliferation of KCs. Conclusion This study provides a new insight into how calcipotriol affects proliferation of keratinocytes by decreasing the expression of EGR1 and PLK2. Furthermore, the results offer groundwork for developing novel compounds for the treatment of hiperproliferative skin disorders like psoriasis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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