Elevated Serum Insulin-like Growth Factor (IGF-1) and IGF Binding Protein-3 Levels in Patients with Systemic Sclerosis: Possible Role in Development of Fibrosis

Abstract

ObjectiveTo examine serum concentrations of insulin-like growth factor (IGF-1) and IGF binding protein (IGFBP-3), a major carrier protein for IGF-1, in patients with systemic sclerosis (SSc); and to relate the results to clinical features in SSc.MethodsSerum IGF-1 and IGFBP-3 levels in 92 Japanese patients with SSc were measured by ELISA. Expression of IGF-1 and IGFBP-3 messenger RNA (mRNA) in the skin was quantified by real-time reverse transcription-polymerase chain reaction.ResultsSerum IGF-1 and IGFBP-3 levels were significantly elevated in patients with SSc compared with patients with systemic lupus erythematosus or healthy controls. IGF-1 levels were higher in patients with diffuse cutaneous SSc (dcSSc) than in patients with limited cutaneous SSc (lcSSc). Patients with increased IGF-1 levels had more severe skin involvement and pulmonary fibrosis. IGF- 1 mRNA was upregulated in the affected skin of patients with SSc. There were no significant differences in serum IGFBP-3 levels between dcSSc and lcSSc. IGFBP-3 levels were not associated with skin thickness and pulmonary fibrosis. Patients with increased IGF-1 or IGFBP-3 had lower frequency of telangiectasia than patients with normal levels.ConclusionThese results suggest that both IGF-1 and IGFBP-3 are involved in the development of SSc. The role of IGF-1 appears to be different from that of IGFBP-3.