Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Surgery, Division of Urology, Sao Paulo Federal University, Sao Paulo, Brazil; CAPES Foundation, Ministry of Education of Brazil, Brasilia, Brazil.
Urology. 2013 Oct;82(4):975.e1-6. doi: 10.1016/j.urology.2013.06.042.
To characterize transforming growth factor beta 1 (TGFβ1) and related signaling pathway proteins in a large cohort of human penile tissue (HPT) samples.
HPT was collected from patients undergoing penile prosthesis implantation for erectile dysfunction (ED) and divided into the following 2 groups: postradical prostatectomy ED (RP-ED; n = 57) and organic ED (O-ED; n = 30). HPT from patients undergoing partial penectomy without ED was used as controls (CON; n = 6). Western blot analysis was performed to investigate the protein expressions of TGFβ1, thrombospondin 1 (TSP1; an activator of TGFβ1), fibronectin (an extracellular matrix glycoprotein induced by TGFβ1), and a family of transcriptional factors activated by TGFβ1 (Smad2, phospho-Smad2-serine-465/467 [pSmad2], Smad3, phospho-Smad3-serine-423/425 [pSmad3]).
Expressions of TGFβ1 and TSP1 were significantly higher in RP-ED (P <.05) and O-ED (P <.05) groups compared with that of the CON group and were not different between either ED groups. Expressions of Smad2, pSmad2, Smad3, pSmad3, and fibronectin were similar among all groups. Within the RP-ED group, a subgroup analysis showed that time from RP to penile prosthesis implantation was related to increased expression of pSmad2 (P <.05), and previous history of intracavernosal injection was related to increased expression of TGFβ1 (P <.05).
Our results demonstrate that TSP1- and TGFβ1-dependent fibrotic changes occur in penile tissue in patients with ED regardless of etiology. The unchanged expression of the Smad transcriptional factors may be reconciled by a Smad-independent downstream signaling pathway transmitting TGFβ1 signals.
对大量人类阴茎组织(HPT)样本中的转化生长因子β 1(TGFβ1)和相关信号通路蛋白进行特征描述。
从因勃起功能障碍(ED)接受阴茎假体植入术的患者中采集 HPT,并将其分为以下 2 组:根治性前列腺切除术后 ED(RP-ED;n=57)和器质性 ED(O-ED;n=30)。将接受非 ED 部分阴茎切除术的患者的 HPT 作为对照(CON;n=6)。通过 Western blot 分析研究 TGFβ1、血小板反应蛋白 1(TSP1;TGFβ1 的激活剂)、纤维连接蛋白(TGFβ1 诱导的细胞外基质糖蛋白)和 TGFβ1 激活的转录因子家族(Smad2、磷酸化 Smad2-丝氨酸 465/467[pSmad2]、Smad3、磷酸化 Smad3-丝氨酸 423/425[pSmad3])的蛋白表达。
与 CON 组相比,RP-ED(P<.05)和 O-ED(P<.05)组中 TGFβ1 和 TSP1 的表达显著升高,而两组 ED 患者之间的表达无差异。Smad2、pSmad2、Smad3、pSmad3 和纤维连接蛋白的表达在所有组之间相似。在 RP-ED 组中,亚组分析显示,从 RP 到阴茎假体植入的时间与 pSmad2 的表达增加相关(P<.05),而腔内注射的既往史与 TGFβ1 的表达增加相关(P<.05)。
我们的研究结果表明,无论病因如何,ED 患者的阴茎组织中都会发生 TSP1 和 TGFβ1 依赖性纤维化改变。Smad 转录因子不变的表达可能通过传递 TGFβ1 信号的 Smad 非依赖性下游信号通路得到协调。