THE EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR GENE IN DUPUYTREN CONTRACTURE

Dupuytren contracture is a disease of the palmar fascia characterized by nodular fibroblastic proliferation; its etiology and pathogenesis a re poorly understood. Growth factors are polypeptides that regulate ce ll growth and differentiation and extracellular matrix production. Pla telet-derived growth factor is known to cause fibroblastic proliferati on, and it may be involved in the pathogenesis of Dupuytren contractur e. The purpose of this study was to determine if the gene for the B ch ain of platelet-derived growth factor is expressed in Dupuytren contra cture. Tissue from patients who had Dupuytren disease was examined imm unohistochemically with the 5B5 antibody, which is a marker for fibrob lasts. Polymerase chain reaction, gel electrophoresis, Southern blotti ng, and in situ hybridization were also used to study gene expression in the tissue as well as in normal fascia, A172 cells, and MRCS cells. Total cellular RNA was extracted from tissue and cells, Polymerase ch ain reaction was done with oligonucleotide primers complementary to a portion of the platelet-derived growth-factor-B and platelet-derived g rowth-factor-receptor genes. The platelet-derived growth-factor-B gene was expressed in all six specimens from the patients who had Dupuytre n contracture as well as in the A172 cells, but not in the normal fasc ia lata or the MRC5 cells. These results were confirmed with Southern blotting of the products of the reaction,vith a platelet-derived growt h-factor-B probe. The gene for the platelet-derived growth-factor rece ptor was expressed by all tissues and cells studied. Immunohistochemic al staining showed that the cells from the patients who had Dupuytren contracture were fibroblasts, and in situ hybridization showed that th ese cells expressed the platelet-derived growth-factor-B gene, Plantar fascia, fascia lata, and transverse palmar fascia (the Skoog fibers) did not express this gene. CLINICAL RELEVANCE: The presence of platele t-derived growth factor B and its receptor in patients who have Dupuyt ren contracture suggests that platelet-derived growth factor B acting through an autocrine and paracrine loop may account for the proliferat ion, contracture, and abnormal biochemistry of fibroblasts in Dupuytre n contracture. Future treatment strategies may be directed at reversin g or counteracting this abnormality in gene expression.