Expression of pituitary tumor-transforming gene-1 and its pathogenic role in systemic sclerosis

Abstract

To investigate the expression of tumor-transforming gene-1 (PTTG1) in systemic sclerosis (SSc) and its role in fibrosis. Skin biopsy samples were collected from 21 patients with SSc and 22 patients with healthy skin for detecting the mRNA and protein expressions of PTTG1 using real-time PCR (RT-PCR) and immunohistochemistry, respectively. In cultured primary human dermal fibroblasts, PTTG1 expression was knocked down via RNA interference (siRNA), and the mRNA expression levels of PTTG1 and the fibrosis-related genes α-SMA, COL1A1, COL1A2, and COL3A1 were detected using RT-PCR; the proliferation of the cells was assessed using a real-time cell proliferation detection system. Compared with those in normal skin samples, the mRNA and protein expressions of PTTG1 increased significantly in the skin tissue of patients with SSc (P < 0.05). In cultured primary skin fibroblasts, the expression of PTTG1 mRNA was positively correlated with those of α-SMA (R2=0.8192, P < 0.05), COL1A1 (R2=0.6398, P < 0.05), COL1A2 (R2=0.316, P < 0.05) and COL3A1 mRNAs (R2=0.3727, P < 0.05). Interference of PTTG1 expression significantly inhibited the cell proliferation, obviously lowered the expressions of fibrosis-related genes, and down-regulated the expression of collagen in the fibroblasts. PTTG1 is highly expressed in skin tissues of patients with SSc, and PTTG1 knockdown can reduce the activity of the dermal fibroblasts, suggesting a close correlation of PTTG1 with fibrosis in SSc.