Abnormal phenotype of in vitro dermal fibroblasts from patients with pseudoxanthoma elasticum (PXE)

Pseudoxanthoma elasticum (PXE) is a genetic connective tissue disease, whos e gene and pathogenesis are still unknown. Dermal fibroblasts from patients affected by PXE have been compared in vitro with fibroblasts taken from se x and age-matched normal individuals. Cells were grown and investigated in monolayer, into three-dimensional collagen gels and in suspension. Compared with normal cells, PXE fibroblasts cultured in monolayer entered more rapi dly within the S phase and exhibited an increased proliferation index; on t he contrary, similarly to normal fibroblasts, PXE cells did not grow in sus pension. Furthermore, compared with normal fibroblasts, PXE cells exhibited lower efficiency in retracting collagen type I lattices and lower adhesion properties to collagen type I and to plasma fibronectin. This behavior was associated with higher expression of integrin subunits alpha 2, alpha 5, a lpha v, whereas beta 1 subunit as well as alpha 2 beta 1 and alpha 5 beta 1 integrin expression was lower than in controls. Compared to controls, PXE fibroblasts had higher CAM protein expression in accordance with their high tendency to form cellular aggregates, when kept in suspension. The demonst ration that PXE fibroblasts have altered cell-cell and cell-matrix interact ions, associated with modified proliferation capabilities, is consistent wi th the hypothesis that the gene responsible for PXE might have a broad regu latory role on the cellular machinery. (C) 2000 Elsevier Science B.V. All r ights reserved.