Proliferating keratinocytes are putative sources of the psoriasis susceptibility-related EDA+ (extra domain A of fibronectin) oncofetal fibronectin.
The extra domain A of fibronectin (EDA+ oncofetal isoform of fibronectin was recently reported to be overexpressed in psoriatic uninvolved epidermis. It has been proposed that the abnormal presence of EDA+ oncofetal protein at the dermal-epidermal junction in the uninvolved skin may provide the "psoriatic" environment in which keratinocytes are in a preactivated state with regard to mitogenic signals (e.g., T cell lymphokines). To determine the possible sources of cellular fibronectin in the non-lesional psoriatic skin, we aimed to investigate whether keratinocytes could produce the EDA+ oncofetal form of fibronectin. RT-PCR studies revealed that both cultured normal keratinocytes and HaCaT cells express the EDA+ splice variant of fibronectin mRNA, and in HaCaT cells the EDA+/EDA- transcript ratio was elevated compared with normal keratinocytes. Cultured keratinocytes and HaCaT cells showed intracytoplasmic staining with an EDA+ fibronectin-specific antibody and among the positively stained cells many showed mitosis. Using RT-PCR, western blot analysis, and flow cytometry, we showed that in synchronized HaCaT cells the amount of both total fibronectin and its EDA+ isoform change with the proliferation/differentiation state of HaCaT cells and peak in highly proliferating cells. We show that in short-term ex vivo cultures, a small population of EDA+ fibronectin containing cell population appear among psoriatic uninvolved, but not normal epidermal cells. We also demonstrate that cell attachment has a strong influence on the expression of both total and EDA+ fibronectin. Our results suggest that proliferating keratinocytes could be the sources of the psoriasis susceptibility-related EDA+ oncofetal fibronectin in the epidermis.
Dermatological Research Group of the Hungarian Academy of Sciences and the University of Szeged, 6720 Szeged, Korányi fasor 6, Hungary. szell@derma.szote.u-szeged-hu
Márta
M
Széll
Zsuzsanna
Z
Bata-Csörgo
Andrea
A
Koreck
Andor
A
Pivarcsi
Hilda
H
Polyánka
Csilla
C
Szeg
Magdolna
M
Gaál
Attila
A
Dobozy
Lajos
L
Kemény
D017398:Alternative Splicing; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology; D000078404:Epidermal Cells; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011565:Psoriasis / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis
D005353:Fibronectins; D012333:RNA, Messenger; C121542:oncofetal fibronectin