Role of connective tissue growth factor in fibronectin synthesis in cultured human prostate stromal cells.

Objectives: To clarify the correlation of connective tissue growth factor (CTGF) expression and fibronectin (FN) synthesis after transforming growth factor-beta-1 (TGF-beta1) stimulation in human prostate stromal cells.

Methods: Primary cultures of human prostate stromal cells were established from nine normal prostates by the explant method. The gene and protein expressions of CTGF and FN after TGF-beta1 treatment were examined. We also investigated the effect of CTGF blockade on TGF-beta1-induced FN synthesis by CTGF antisense oligodeoxynucleotide treatment.

Results: CTGF expression was detected in all nine prostate stromal cells by reverse transcriptase-polymerase chain reaction and immunoblotting. In prostatic tissues, CTGF expression was observed more strongly in epithelial cells than in the stromal area by immunohistochemistry. The upregulation of both CTGF and FN protein by TGF-beta1 treatment was demonstrated in a dose-dependent manner. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated FN synthesis.

Conclusions: CTGF plays a crucial role in extracellular matrix production as a TGF-beta1 downstream mediator in human prostate stromal cells, suggesting that CTGF blockade is likely to be a therapeutic target against benign prostatic hyperplasia.