Phenotypical and Functional Differences in Germinative Subpopulations Derived from Normal and Psoriatic Epidermis

Abstract

A model that explains how maintenance of normal homeostasis in human epidermis is achieved describes a heterogeneous cell population of stem cells (SC) and transit amplifying cells (TAC). There must be a tightly regulated balance between SC self-renewal and the generation of TAC that undergo a limited number of divisions before giving rise to postmitotic, terminally differentiated cells. To investigate whether this balance is disturbed in psoriatic epidermis, we have characterized flow sorted enriched SC and TAC using immunocytochemistry, flow cytometry, and real-time quantitative PCR. Our data demonstrate phenotypical and functional differences in SC (beta(1)-integrin bright) and TAC (beta(1)-integrin dim) enriched fractions between normal and psoriatic keratinocytes. Some of these were expected, such as mRNA levels of keratins 6 and 10 and of the Ki-67 antigen. Most remarkable were differences in phenotype of the psoriatic TAC compared with TAC from normal skin. These subpopulations also displayed striking differences following culture. Downregulation of markers associated with the regenerative phenotype (psoriasin, elafin, psoriasis-associated fatty acid binding protein) in cultured psoriatic dim cells in the absence of hyperproliferation suggests that proliferation and regenerative maturation are coupled. From these results, in combination with our earlier findings, we propose a model for epidermal growth control in which TAC play a crucial role.

p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes

“…40 The inherent malfunction in the behavior of this sub-population is enforced by altered levels of a number of markers in TA from psoriatic lesions as compared with TA from normal skin. 41 This work demonstrates that the most remarkable reduction in p75NTR expression was detected in TA cells. This finding, together with the lesser susceptibility to apoptosis of psoriatic TA cells, strongly indicates that alteration of TA cells in psoriasis is partly based on a defect in p75NTR.…”

Influence of phototherapy in psoriasis on ki-67 antigen expression: a preliminary study

“…In psoriatic lesions, the expression is observed in a greater number of keratinocytes of the basal layer. Moreover, it is also observed in nuclei of suprabasal cells [13,15,[17][18][19][20][21].…”

“…Epidermal hyperproliferation is connected with intense cell proliferation in the basal layer and too rapid, thus irregular keratinocyte maturation. In the healthy epidermis proliferation affects only a small number of cells of the basal layer, whereas in psoriasis, a great number of basal keratinocytes are in the division phase [13]. Improper proliferation and keratinization as well as deviation with regards to cell-cycle length and keratinocyte survival time are reflected in irregular expression of various molecules which are markers of these processes: Ki-67 protein and proliferating cell nuclear antigen (PCNA) (proliferation) as well as cytokeratins, such as CK6 or CK16 (differentiation) [14].…”

Psoriasis Risk Genes of the Late Cornified Envelope-3 Group Are Distinctly Expressed Compared with Genes of Other LCE Groups

“…14 The reverse transcriptase reaction products were used for qPCR amplification of genes of interest using a quantification system (MyiQ Single-Color Real-Time Detection System; Bio-Rad Laboratories, Inc.) and melting curve analysis as described previously. 15 Expression of target genes was normalized to expression of the housekeeping gene human ribosomal phosphoprotein P0 (RPLP0) in the same sample. For analysis of LCE1A, LCE1C, LCE1D and LCE1E, and the complete LCE2 group, primers were used as described previously.…”