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Calcipotriol Affects Keratinocyte Proliferation by Decreasing Expression of Early Growth Response-1 and Polo-like Kinase-2

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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.

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Acknowledgements

The authors wish to express their appreciation to Professor Roger Pain for critical review of the manuscript.

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Authors and Affiliations

  1. Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia

    Jernej Kristl, Petra Slanc & Borut Štrukelj

  2. Tissue Typing Center, Blood Transfusion Centre of Slovenia, Šlajmerjeva 6, 1000, Ljubljana, Slovenia

    Metka Krašna & Matjaž Jeras

  3. Department of Biotechnology, Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia

    Aleš Berlec

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  1. Jernej Kristl
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Correspondence to Jernej Kristl.

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Kristl, J., Slanc, P., Krašna, M. et al. Calcipotriol Affects Keratinocyte Proliferation by Decreasing Expression of Early Growth Response-1 and Polo-like Kinase-2. Pharm Res 25, 521–529 (2008). https://doi.org/10.1007/s11095-007-9388-z

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  • DOI: https://doi.org/10.1007/s11095-007-9388-z

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