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

World J Urol. 2009 Feb;27(1):123-30. doi: 10.1007/s00345-008-0320-x. Epub 2008 Aug 14.

Abstract

Introduction: 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.

Materials and methods: 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.

Results: 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.

Conclusion: In conclusion, analysis of MCP-1 expression might be a useful marker for Peyronie's disease.

MeSH terms

  • 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*

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • RNA, Messenger
  • SMAD7 protein, human
  • Smad7 Protein
  • Transforming Growth Factor beta1