BACKGROUND IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the underlying molecular mechanisms of ADSCs and ICAII in this process remain largely unclear. METHODS ADSCs were treated with different concentrations of ICAII. Cell proliferation was determined by MTT assay. qRT-PCR and western blot were performed to detect expressions of SCs markers, signal transducer and activator of transcription-3 (STAT3), and microRNA-let-7i (let-7i). Luciferase reporter assay was conducted to verify the regulatory relationship between let-7i and STAT3. The detection of intracavernosal pressure (ICP) and the ratio of ICP/mean arterial pressure (MAP) were used to evaluate the EF in bilateral cavernous nerve injury (BCNI) rat models. RESULTS ICAII promoted cell proliferation of ADSCs in a dose-dependent manner. The mRNA and protein levels of SCs markers were increased by ICAII treatment in a dose-dependent manner in ADSCs. Moreover, let-7i was significantly decreased in ICAII-treated ADSCs and upregulation of let-7i attenuated ICAII-induced promotion of SCs markers. In addition, STAT3 was a direct target of let-7i and upregulated in ICAII-treated ADSCs. Interestingly, overexpression of STAT3 abated the let-7i-mediated inhibition effect on differentiation of ADSCs to SCs and rescued the ICAII-mediated promotion effect on it. Besides, combination treatment of ADSCs and ICAII preserved the EF of BCNI rat models, which was undermined by let-7i overexpression. CONCLUSION ICAII was effective for preserving EF by promoting the differentiation of ADSCs to SCs via modulating let-7i/STAT3 pathway.

中文翻译：

---

IcarisideII通过let-7i / STAT3轴促进ADSC向SC的分化，以保持勃起功能。

背景伊卡甙II（ICAII）可以促进脂肪组织干细胞（ADSCs）向雪旺细胞（SCs）的分化，从而改善勃起功能（EF），并为治疗勃起功能障碍（ED）提供现实的治疗选择。但是，ADSCs和ICAII在此过程中的潜在分子机制仍不清楚。方法用不同浓度的ICAII处理ADSC。细胞增殖通过MTT测定法确定。进行qRT-PCR和western blot检测SCs标记，信号转导和转录激活因子3（STAT3）和microRNA-let-7i（let-7i）的表达。进行荧光素酶报告基因测定以验证let-7i和STAT3之间的调节关系。海绵体腔内压力（ICP）和ICP /平均动脉压之比（MAP）的检测用于评估双侧海绵体神经损伤（BCNI）大鼠模型中的EF。结果ICAII以剂量依赖的方式促进了ADSC的细胞增殖。通过ICAII处理，ADSC中SCs标志物的mRNA和蛋白质水平以剂量依赖性方式增加。此外，let-7i在ICAII处理的ADSC中显着降低，let-7i的上调减弱了ICAII诱导的SCs标记的促进。另外，STAT3是let-7i的直接靶标，并且在ICAII处理的ADSC中被上调。有趣的是，STAT3的过度表达减弱了let-7i介导的对ADSCs向SCs分化的抑制作用，并挽救了ICAII介导的对其的促进作用。除了，ADSCs和ICAII的联合治疗保留了BCNI大鼠模型的EF，这被let-7i过表达所破坏。结论ICAII可通过调节let-7i / STAT3途径促进ADSCs向SCs的分化来有效维持EF。