Hepatocyte growth factor-modified adipose tissue-derived stem cells improve erectile function in streptozotocin-induced diabetic rats.
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.
a Yijishan Hospital of Wannan Medical College , Wuhu , China.
Tao
T
Liu
a Yijishan Hospital of Wannan Medical College , Wuhu , China.
Yifeng
Y
Peng
a Yijishan Hospital of Wannan Medical College , Wuhu , China.
Chao
C
Jia
a Yijishan Hospital of Wannan Medical College , Wuhu , China.
Xiang
X
Fang
a Yijishan Hospital of Wannan Medical College , Wuhu , China.
Jing
J
Li
a Yijishan Hospital of Wannan Medical College , Wuhu , China.
Wan
W
Zhong
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D007172:Erectile Dysfunction / Q000209:etiology / Q000628:therapy*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D017228:Hepatocyte Growth Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C498862:Acta2 protein, rat
Adipose tissue-derived stem cell; diabetes; erectile function; hepatocyte growth factor