Liu Tao, Peng Yifeng, Jia Chao, Fang Xiang, Li Jing, Zhong Wan
a Yijishan Hospital of Wannan Medical College , Wuhu , China.
Growth Factors. 2015;33(4):282-9. doi: 10.3109/08977194.2015.1077825. Epub 2015 Sep 4.
TGFβ1-Smad signaling pathway is closely related to various tissues fibrosis. Hepatocyte growth factor (HGF) has been shown to antagonize TGFβ1-Smad signaling and may improve kidney tissue fibrosis in diabetic models. Penile fibrosis is a pathological condition which occurs during diabetic erectile dysfunction (ED). The aim of this study was to examine the effect of the treatment of ED in diabetic rats with a combination of HGF and adipose tissue-derived stem cells (ADSC). In this diabetes model, rats were injected intraperitoneally with 60 mg streptozotocin (STZ) to induce diabetes. Three months later, the diabetic rats were divided into a negative control(NC) group, an ADSC-treated group and an ADSC + HGF-treated group while normal rats were assigned into a sham group. Rats in the sham and NC groups were injected in the corpus cavernosum with phosphate-buffered saline, while rats in the other groups were injected with either ADSC or ADSC + HGF. One month later, erectile function was examined in each group and penile tissues were collected for experiments. The expression of smooth muscle actin (SMA) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) was analyzed by Western blotting. The smooth muscle and collagen deposition in corpus cavernosum was evaluated by Masson staining, while endothelial changes were assessed immunohistochemically. Cell apoptosis was detected by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. The results revealed that ADSC alone can significantly improve erectile function in diabetic rats, but in combination with HGF the improvement was more prominent, showing higher content of smooth muscle and endothelial cells and lower cell apoptotic index in corpus cavernosum. Treatment with HGF can significantly enhance the beneficial effect of ADSC on erectile function in diabetic rats, and this effect might be closely related to the down-regulation of TGFβ1-Smad signaling.
转化生长因子β1（TGFβ1）-Smad信号通路与各种组织纤维化密切相关。肝细胞生长因子（HGF）已被证明可拮抗TGFβ1-Smad信号通路，并可能改善糖尿病模型中的肾组织纤维化。阴茎纤维化是糖尿病性勃起功能障碍（ED）期间发生的一种病理状况。本研究的目的是研究HGF与脂肪组织来源的干细胞（ADSC）联合治疗糖尿病大鼠ED的效果。在该糖尿病模型中，给大鼠腹腔注射60mg链脲佐菌素（STZ）以诱导糖尿病。三个月后，将糖尿病大鼠分为阴性对照组（NC组）、ADSC治疗组和ADSC+HGF治疗组，而正常大鼠分为假手术组。假手术组和NC组大鼠在海绵体内注射磷酸盐缓冲盐水，而其他组大鼠注射ADSC或ADSC+HGF。一个月后，检测每组大鼠的勃起功能，并收集阴茎组织进行实验。通过蛋白质免疫印迹法分析平滑肌肌动蛋白（SMA）和血小板内皮细胞黏附分子-1（PECAM-1）的表达。采用Masson染色评估海绵体内平滑肌和胶原沉积，采用免疫组织化学法评估内皮变化。通过TdT介导的dUTP缺口末端标记（TUNEL）法检测细胞凋亡。结果显示，单独使用ADSC可显著改善糖尿病大鼠的勃起功能，但与HGF联合使用时改善更显著，海绵体内平滑肌和内皮细胞含量更高，细胞凋亡指数更低。HGF治疗可显著增强ADSC对糖尿病大鼠勃起功能的有益作用，且这种作用可能与下调TGFβ1-Smad信号通路密切相关。
