Differential expression of D-type cyclins in HaCaT keratinocytes and in psoriasis.
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 alpha5-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 alpha5-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.
Belsõ
Nóra
N
Department of Dermatology and Allergology, Faculty of Medicine, University of Szeged, Szeged, Hungary. noribels@mail.derma.szote.u-szeged.hu
Széll
Márta
M
Pivarcsi
Andor
A
Kis
Kornélia
K
Kormos
Bernadett
B
Kenderessy
Anna Sz
AS
Dobozy
Attila
A
Kemény
Lajos
L
Bata-Csörgõ
Zsuzsanna
Z
D001706:Biopsy; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D056741:Cyclin D; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics*; D004817:Epidermis / Q000473:pathology; D016193:G1 Phase / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D011565:Psoriasis / Q000473:pathology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D016196:S Phase / Q000502:physiology
C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056741:Cyclin D; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; D039482:Integrin alpha5; D012333:RNA, Messenger