ESTABLISHMENT OF PENILE FIBROSIS MODEL USING MOUSE NIH3T3 FIBROBLASTS EXPRESSING TRANSFORMING GROWTH FACTOR-β1

초록

INTRODUCTION AND OBJECTIVES: This study was undertaken to establish chronic rat model with cavernous fibrosis using mouse NIH3T3 fibroblasts, which express TGF-β1 (NIH3T3-TGF-β1 cell). MATERIALS AND METHODS: Sixty-nine male Sprague-Dawley rats were subjected to intracavernous injection of solutions (0.1 ml) and classified into three groups: Group 1; those receiving culture media (n=10), Group 2; those receiving recombinant human TGF-β1 (200 ng, n=10), Group 3; those receiving NIH3T3-TGF-β1 cells (3x106 cells, n=49). The penis was sequentially removed. We performed immunohistochemical staining for smooth muscle actin, TGF-β1 and its type II receptor to quantitatively evaluate smooth muscle and to evaluate the expression of both TGF-β1 and its receptor in corpus cavernosa by scoring intensity of immunoreactivity (score: from 0 to 3). RESULTS: Masson’s trichrome staining revealed that fibrotic nodules appeared from 15 days to 20 days after injection of NIH3T3-TGF-β1 cells, which were gradually decreased and disappeared at 40 days after injection. In contrast, no evidences of cavernous fibrosis were identified in group 1 and 2. TGF-β1 expression was significantly increased in group 3 (2.2±0.6), compared to group 1 (0.5±0.7) or 2 (0.4±0.5) (P<0.001). Type II receptor expression was also significantly increased in group 3 (2.7±0.5), compared to group 1 (1.2±0.6) or 2 (1.1±0.3) (P<0.001). Content of cavernous smooth muscle was significantly increased in group 3 (15.2±3.7%), especially around the fibrotic nodules, compared to group 1 (8.9±3.2%) and 2 (8.9±1.3%) (P<0.001). CONCLUSIONS: NIH3T3-TGF-β1 cell sufficiently induced relatively long-lasting cavernous fibrosis. This model may contribute to further investigation of the pathogenesis of penile fibrosis associated with TGF-β1 signal and development of new therapeutics targeting this signal transduction.