Liang Li, Zheng Dachao, Lu Chao, Xi Qinghong, Bao Hua, Li Wengfeng, Gu Yufei, Mao Yuanshen, Xu Bin, Gu Xin
Department of Respiratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, China.
Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201999, China.
Stem Cell Res Ther. 2021 Jan 25;12(1):87. doi: 10.1186/s13287-021-02161-8.
Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED.
In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs).
Our data showed that miR-301a-3p-enriched exosome treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha smooth muscle actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p.
Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered a new therapeutic target for treating ED associated with OSA.
阻塞性睡眠呼吸暂停（OSA）患者常出现勃起功能障碍（ED）。对脂肪间充质干细胞（ADSC）来源的外泌体的研究表明，它们在包括ED在内的许多疾病中具有显著的治疗作用。
在本研究中，通过慢性间歇性缺氧（CIH）暴露在Sprague Dawley（SD）大鼠中诱导ED。然后在海绵体平滑肌细胞（CCSMC）中测量CIH介导的影响。
我们的数据表明，富含miR-301a-3p的外泌体治疗通过促进自噬和抑制细胞凋亡，显著恢复了大鼠和CCSMC中的勃起功能。该治疗还显著恢复了大鼠和CCSMC中α平滑肌肌动蛋白（α-SMA）的水平。生物信息学预测磷酸酶和张力蛋白同源物（PTEN）和Toll样受体4（TLR4）可能是miR-301a-3p的靶标。
我们的结果表明，PTEN过表达载体或TLR4过表达载体逆转了miR-301a-3p在CCSMC中所实现的治疗效果，表明PTEN/缺氧诱导因子-1α（HIF-1α）和TLR4信号通路在ED的进展中起关键作用。本研究结果表明，miR-301a-3p应被视为治疗与OSA相关的ED的新治疗靶点。
