Transplantation of Human Urine-Derived Stem Cells Ameliorates Erectile Function and Cavernosal Endothelial Function by Promoting Autophagy of Corpus Cavernosal Endothelial Cells in Diabetic Erectile Dysfunction Rats
Autor: | Chi Zhang, Daosheng Luo, Tingting Li, Qiyun Yang, Yun Xie, Haicheng Chen, Linyan Lv, Jiahui Yao, Cuncan Deng, Xiaoyan Liang, Rongpei Wu, Xiangzhou Sun, Yuanyuan Zhang, Chunhua Deng, Guihua Liu |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: | |
Zdroj: | Stem Cells International, Vol 2019 (2019) |
Druh dokumentu: | article |
ISSN: | 1687-966X 1687-9678 |
DOI: | 10.1155/2019/2168709 |
Popis: | Aims. Cavernosal endothelial dysfunction is one of the factors in developing diabetic erectile dysfunction (DED), but the mechanism of cavernosal endothelial dysfunction is unclear. The present study is aimed at determining the contribution of autophagy in cavernosal endothelial dysfunction of DED rats and explaining the therapeutic effect of urine-derived stem cells (USCs). Methods. After rat corpus cavernosal vascular endothelial cells (CCECs) were isolated and cultured in vitro, CCECs were treated with advanced glycation end products (AGEs) to mimic the diabetic situation. Autophagy flux, proliferation, and apoptosis of CCECs were determined by mRFP-GFP-LC3 adenovirus infection combined with fluorescence observation and western blot analysis. USCs were isolated from the urine of six healthy male donors, and coculture systems of USCs and CCECs were developed to assess the protective effect of USCs for CCECs in vitro. The contribution of autophagy to the cellular damage in CCECs was evaluated by the autophagic inhibitor, 3-methyladenine (3-MA). Then, DED rats were induced by streptozotocin (50 mg/kg) and screened by apomorphine test (100 μg/kg). In DED rats, USCs or PBS as vehicle was administrated by intracavernous injection (n=15 per group), and another 15 normal rats served as normal controls. Four weeks after injection, erectile function was evaluated by measuring the intracavernosal pressure (ICP) and mean arterial pressure (MAP). Cavernosal endothelial function and autophagic activity were examined by western blot, immunofluorescence, and transmission electron microscopy. Results. In vitro, AGE-treated CCECs displayed fewer LC3 puncta formation and expressed less LC3-II, Beclin1, and PCNA but expressed more p62 and cleaved-caspase3 than controls (p |
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