Upregulation of monocyte chemoattractant protein 1 and effects of transforming growth factor-beta 1 in Peyronie's disease

Biochem Biophys Res Commun. 2002 Jul 26;295(4):1014-9. doi: 10.1016/s0006-291x(02)00765-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemokine CCL2 / metabolism*
  • Connective Tissue Growth Factor
  • Fibroblasts / metabolism
  • Growth Substances / metabolism*
  • Humans
  • Immediate-Early Proteins / metabolism*
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins*
  • Male
  • Penile Induration / metabolism*
  • RNA / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1
  • Up-Regulation*

Substances

  • CCN2 protein, human
  • CCN2 protein, rat
  • Chemokine CCL2
  • Growth Substances
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • TGFB1 protein, human
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Connective Tissue Growth Factor
  • RNA