Differential Expression of D-Type Cyclins in HaCaT Keratinocytes and in Psoriasis

• Published in: Journal of investigative dermatology Vol. 128; no. 3; pp. 634 - 642
• Main Authors: Belsõ, Nóra, Széll, Márta, Pivarcsi, Andor, Kis, Kornélia, Kormos, Bernadett, Kenderessy, Anna Sz, Dobozy, Attila, Kemény, Lajos, Bata-Csörgõ, Zsuzsanna
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.03.2008; Nature Publishing; Elsevier Limited
• Subjects: Antibodies; Biological and medical sciences; Biopsy; Cell cycle; Cell Division - physiology; Cell Line, Transformed; Cell proliferation; Cyclin D; cyclin D1; Cyclin D2; Cyclin D3; Cyclins - genetics; Cytology; Data processing; Dermatology; Differentiation; Epidermis; Epidermis - pathology; G1 Phase - physiology; Gene expression; Gene Expression - physiology; Humans; Integrin alpha5 - metabolism; Internet; Keratinocytes; Keratinocytes - cytology; Keratinocytes - physiology; Medical sciences; Psoriasis; Psoriasis - pathology; Psoriasis - physiopathology; Psoriasis. Parapsoriasis. Lichen; Resting Phase, Cell Cycle - physiology; RNA, Messenger - metabolism; S phase; S Phase - physiology; Cyclin; Keratinocyte; Skin disease; Psoriasis; Dermatology; Cell cycle
• ISSN: 0022-202X; 1523-1747; 1523-1747
• DOI: 10.1038/sj.jid.5701059

In this study, we show that the G0–G1/S phase of HaCaT keratinocyte cell cycle is characterized by D1-type cyclin expression, whereas during the repeated rapid turnover of highly proliferating cells, the expression of cyclins D2 and D3 dominates. Knocking down cyclin D1 mRNA resulted in no change of cell proliferation and morphology, indicating that D2 and D3 cyclins could substitute for D1 in driving the cell cycle. Increased numbers of cyclin D1-expressing keratinocytes were found in the basal layers of the lesional psoriatic epidermis compared to both normal and non-lesional epidermis without increased expression of cyclin D1 mRNA, suggesting a possible dysfunction in the degradation of cyclin D1 protein. We also detected a significant increase in cyclin D2 and D3 mRNA expressions in psoriatic epidermis compared to normal epidermis with no difference in protein expressions. Blocking α5-integrin function by a neutralizing antibody in HaCaT keratinocytes downregulated the expression of cyclin D1 mRNA without affecting the expressions of cyclin D2 and D3 indicating a regulatory role for α5-integrin in the expression of cyclin D1. Our data suggest a possible role for D-type cyclins in the excessive basal-cell proliferation and perturbed keratinocyte differentiation in the psoriatic epidermis.