Upregulation of mRNA expression of MCP-1 by TGF-beta1 in fibroblast cells from Peyronie's disease

• Published in: World journal of urology Vol. 27; no. 1; pp. 123 - 130
• Main Authors: Szardening-Kirchner, Carolin, Konrad, Lutz, Hauck, Ekkehard W, Haag, Simone M, Eickelberg, Oliver, Weidner, Wolfgang
• Format: Journal Article
• Language: English
• Published: Germany 01-02-2009
• Subjects: Cells, Cultured; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Fibroblasts - metabolism; Humans; Male; Penile Induration - genetics; Penile Induration - metabolism; RNA, Messenger - biosynthesis; Smad7 Protein - biosynthesis; Transforming Growth Factor beta1 - biosynthesis; Transforming Growth Factor beta1 - genetics; Up-Regulation
• ISSN: 1433-8726
• DOI: 10.1007/s00345-008-0320-x

Peyronie's disease (PD) is a localized connective tissue disorder of the penile tunica albuginea (TA) with a still obscure etiopathology. Recent studies from our laboratory have demonstrated differences in Smad3 and Smad4 gene expression of PD-fibroblasts and non-PD-fibroblasts after stimulation with recombinant TGF-beta1 for 1 h. In the present study, we investigated gene expression of Smad2-Smad4 and Smad7 up to 6 h after stimulation with TGF-beta1. As a positive control, MCP-1 gene expression was monitored.
Cells with fibroblast characteristics were isolated from seven PD plaques and three TA controls. The cells were incubated with recombinant TGF-beta1 for 2-6 h and expression of Smad2-Smad4, Smad7, and monocyte chemotactic protein-1 (MCP-1) was determined by quantitative real-time PCR.
TGF-beta1 treatment resulted in a statistically significant up-regulation of Smad7 and MCP-1 gene expression. Smad7 expression was increased after 2 h (P < 0.001) and was still high after 4 h (P < 0.05). No significant differences between fibroblasts from PD-patients compared to non-PD-patients were observed. MCP-1 peaked after 4 h (P < 0.001) and remained high up to 6 h (P < 0.01). PD-fibroblasts revealed a significantly increased MCP-1 gene expression compared to non-PD-fibroblasts (P = 0.013) after 2 h and remained significantly different also after 6 h (P = 0.038). Gene expression of Smad2-Smad4 did not change during stimulation with TGF-beta1.
In conclusion, analysis of MCP-1 expression might be a useful marker for Peyronie's disease.