Enhanced insulin-like growth factor finding protein-related protein 2 (connective tissue growth factor) expression in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis

Connective tissue growth factor is a recently described chemoattractant and fibroblast mitogen which, because of sequence homology and weak binding to insulin-like growth factor (IGF)-1, has been proposed as the eighth member of the IGF binding protein (IGFBP) superfamily, named IGFBP-related protei n 2 (IGFBP-rP2). Previous studies have implicated IGFBP-rP2 in a number of heterogeneous fibrotic pathologies, including renal fibrosis, dermal sclero derma, and bleomycin-induced pulmonary fibrosis in mice. Because profibroge nic cytokines may be produced by inflammatory cells, we developed a multipl ex competitive reverse transcription/polymerase chain reaction to quantify IGFBP-rP2 transcripts in bronchoalveolar lavage cells from healthy subjects and patients with idiopathic pulmonary fibrosis (IPF) and pulmonary sarcoi dosis. IGFBP-rP2 messenger RNA expression was enhanced > 10-fold (P < 0.003 ) in patients with IPF; > 40-fold (P < 0.006) in stage I/II sarcoidosis pat ients, and > 90-fold (P < 0.005) in stage III/IV sarcoidosis patients by co mparison with healthy nonsmoking control subjects. We suggest these increas es are predominantly associated with lymphocyte- and neutrophil-driven IGFB P-rP2 production. These findings, together with previous reports implicatin g other IGFBPs in the pathogenesis of pulmonary fibrosis, suggest that the complex network of IGFBPs within the human lung is an important determinant of the outcome of the fibroproliferative response to injury. Allen, J, T., R. A. Knight, C. A. Bloor, and M. A. Spiteri. 1999. Enhanced insulin-like growth factor binding protein-related protein 2 (connective tissue growth f actor) expression in patients with idiopathic pulmonary, fibrbsis and pulmo nary sarcoidosis.