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


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.


CONCLUSIONS
In conclusion, analysis of MCP-1 expression might be a useful marker for Peyronie's disease.
Szardening-Kirchner
Carolin
C
Department of Urology, Medical Faculty, University Hospital Giessen, Justus Liebig University, Rudolf-Buchheim-Str. 7, 35392, Giessen, Germany.
Konrad
Lutz
L
Hauck
Ekkehard W
EW
Haag
Simone M
SM
Eickelberg
Oliver
O
Weidner
Wolfgang
W
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D010411:Penile Induration / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051906:Smad7 Protein / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D012333:RNA, Messenger; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1