Expression of cavernous transforming growth factor‐β₁ and its Type II Receptor in patients with erectile dysfunction

Abstract

It has been hypothesized that transforming growth factor-beta1 (TGF-beta1) signalling is involved in erectile dysfunction (ED). This study was undertaken to elucidate in detail whether expression of TGF-beta1 and its type II receptor is clinically related to various causes of ED. Fifty-four patients with ED and 24 potent men were the subjects of this study. After multidisciplinary work-up, the ED was classified as psychogenic (n = 6), neurogenic (n = 15), or vasculogenic (n = 33). In every subject, percutaneous cavernous biopsy was performed using a Biopty gun. Masson's trichrome staining was used to quantitate collagen fibres and immunohistochemical staining to evaluate both TGF-beta1 and its type II receptor by scoring the intensity of immunoreactivity (score 0-6). Collagen fibres were significantly more abundant in men with vasculogenic ED (72.7 +/- 17.7%) than in control subjects (43.3 +/- 11.2%) or those with psychogenic (45.0 +/- 12.2%) or neurogenic (51.3 +/- 20.3%) ED (p < 0.01). Expression of TGF-beta1 was significantly greater in vasculogenic ED (4.3 +/- 1.3) than in the control subjects (2.4 +/- 0.9) or psychogenic ED (2.0 +/- 0.6) groups (p < 0.01). Type II receptor expression was also significantly increased in vasculogenic ED (3.9 +/- 1.3) compared with control (2.2 +/- 0.7) and psychogenic (2.2 +/- 0.8) or neurogenic (2.6 +/- 1.3) ED (p < 0.01). Of the ED groups, both the hyperlipidaemia and the atherosclerosis patients showed significantly more fibrosis than those without the condition (p < 0.05). The abundance of collagen fibres correlated well with both TGF-beta1 expression (gamma = 0.81; p < 0.001) and receptor II expression (gamma = 0.83; p < 0.001). These results suggest that TGF-beta1 and its receptor II pathway are involved in cavernous fibrosis and ED in man. Patients with vascular risk factors such as hyperlipidaemia and atherosclerosis are liable to ED by activation of this pathway.

Erectile tissue molecular alterations with aging—differential activation of the p42/44 MAP Kinase pathway

“…Furthermore, it was reported that p42/44 kinase is a downstream effector of the transforming growth factor-beta 1 (TGF-b1) signaling pathway (He et al 2010). TGF-b1 expression is increased in aging trabecular fibroblasts and reported to be the main stimulator of collagen synthesis, inducing cavernosal fibrosis and promoting ED (Ferrini et al 2007;Ryu et al 2004). We hypothesize that increased p42/44 activation in aged ECM component may be a downstream event of the TGF-b1 pathway, adding a new piece in the complex puzzle of aging CC signaling events.…”

Oxidative Stress and Molecular Reactions in Arteriogenic Erectile Dysfunction

“…[32][33][34] Clinical studies have shown that cavernosal TGFbeta1 expression is significantly greater in vasculogenic ED patients than in the control subjects or psychogenic ED patients. 35 TGF-beta1 type II receptor expression was also found to be significantly greater in vasculogenic ED compared with control subjects and patients with psychogenic and neurogenic ED. 35 Patients with vascular risk factors such as hyperlipidemia and atherosclerosis were found to have significantly greater degrees of cavernosal fibrosis than those without these conditions.…”

“…35 TGF-beta1 type II receptor expression was also found to be significantly greater in vasculogenic ED compared with control subjects and patients with psychogenic and neurogenic ED. 35 Patients with vascular risk factors such as hyperlipidemia and atherosclerosis were found to have significantly greater degrees of cavernosal fibrosis than those without these conditions. 35 Furthermore, this study has shown that the abundance of collagen fibers closely correlates with both TGF-beta1 and TGF-beta1 receptor II expression, suggesting a role of TGF-beta1 and its receptor II in cavernosal fibrosis in vasculogenic ED patients.…”

“…35 Furthermore, this study has shown that the abundance of collagen fibers closely correlates with both TGF-beta1 and TGF-beta1 receptor II expression, suggesting a role of TGF-beta1 and its receptor II in cavernosal fibrosis in vasculogenic ED patients. 35 Exogenous treatment with TGF-beta has been shown to induce a 2.5-to 4.5-fold increase in the synthesis of types I and III collagen. 36 This effect was reduced by adding the eicosanoid PGE1.…”

“…35 Patients with vascular risk factors such as hyperlipidemia and atherosclerosis were found to have significantly greater degrees of cavernosal fibrosis than those without these conditions. 35 Furthermore, this study has shown that the abundance of collagen fibers closely correlates with both TGF-beta1 and TGF-beta1 receptor II expression, suggesting a role of TGF-beta1 and its receptor II in cavernosal fibrosis in vasculogenic ED patients. 35 Exogenous treatment with TGF-beta has been shown to induce a 2.5-to 4.5-fold increase in the synthesis of types I and III collagen.…”