Synthesis and degradation of connective tissue macromolecules in pachydermoperiostosis (PDF): evidence for altered processing of plasminogen activator inhibitor-1 (PAI-1)

Abstract Pachydermoperiostosis (POP) is a hereditary disease with hy-perostosis, clubbing of fingers, coarse skin and thickening of bones. Previous studies have disclosed some abnormality in the connective tissue in these patients. The purpose of the present study was to investigate connective tissue pathology in one family with PDP using libroblasl cultures. Fibroblastic cells were established from both the affected and healthy looking skin of 2 patients with PDP, and the expression of types I and III collagen, 92 kDa and 72 kDa gelatinases, metalloproteinase inhibitor (TIMP-1), human retinoic acid receptor and transforming growth factor β (TGFβ) was analyzed. The modulation of glycoprolein synthesis, and of plasminogen activators and their inhibitors by TGFβin vitro were also studied. The results indicated that collagen genes and gelatinases were similarly expressed in PDP and control cells, as well as the human retinoic acid receptor. TGF-β stimulated, both in PDP cells and normal cells, the synthesis of fibroneclin, procollagen and plasminogen activator inhibitor-1 (PAI-1), but qualitative differences could not be found. Proteolytically processed forms of PAI-1 were detected in PDP cell lines.