Upregulation of monocyte chemoattractant protein 1 and effects of transforming growth factor-beta 1 in Peyronie's disease.
Peyronie's disease (PD) is characterized by fibrosis in the tunica albuginea (TA) of the penis, which becomes bent as a result. We have previously shown that transforming growth factor-beta 1 (TGF-beta1) is upregulated in the TA of patients with PD and can initiate PD-like lesions in rat models. In this study we isolated three types of fibroblasts: P cells from the lesions of PD patients, C cells from the normal-appearing areas of the TA of the same patients, and N cells from the TA of patients without PD. We examined these cells for the expression of two fibrogenic cytokines, connective tissue growth factor (CTGF), and Monocyte Chemoattractant Protein 1 (MCP-1). We found that CTGF was expressed at similar levels in P, C, and N cells, whereas MCP-1 was significantly more expressed in P cells than in C cells and more in C cells than in N cells. Higher MCP-1 expression was also found in the lesions than in normal TA. Treatment with TGF-beta1-induced higher expression of MCP-1 but not CTGF in all three types of cells, with C cells being the most responsive. Based on these observations, we propose that MCP-1 could be a novel therapeutic target in PD.
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143-1695, USA. clin@urol.ucsf.edu
Ching Shwun
CS
Lin
Guiting
G
Lin
Zhong
Z
Wang
Suzan A
SA
Maddah
Tom F
TF
Lue
D018932:Chemokine CCL2 / Q000378:metabolism*; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010411:Penile Induration / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D018932:Chemokine CCL2; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D012313:RNA