二氢杨梅素通过调节 miR-33/GDNF 轴促进脂肪间充质干细胞向施万细胞分化并恢复勃起功能障碍。
Icariside II facilitates the differentiation of ADSCs to schwann cells and restores erectile dysfunction through regulation of miR-33/GDNF axis.
机构信息
Department of Urology, Institute of Andrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Urology, Institute of Andrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
出版信息
Biomed Pharmacother. 2020 May;125:109888. doi: 10.1016/j.biopha.2020.109888. Epub 2020 Feb 14.
BACKGROUND
Adipose derived stem cells (ADSCs) have the property to differentiate into neuron-like cells, which may provide a novel insight for the restoration of erectile dysfunction (ED) mainly induced by cavernous nerve injury. Icariside II (ICA II) has been reported to play a key role in the regulation of erectile function via stimulating the differentiation of ADSCs to Schwann Cells (SCs). However, the function and molecular mechanisms of ICA II in ED remains to be further clarified.
METHODS
The expression of S100, P75, GDNF and miR-33 was detected by qRT-PCR. And the relative proteins expression was determined by western blot. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. Bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the interaction between miR-33 and GDNF. Intracavernosal pressure (ICP), the ratio of ICP and mean arterial pressure (MAP), as well as nNOS expression were examined to evaluate the erectile function of SD rats with bilateral cavernous nerve injury (BCNI).
RESULTS
ICA II and miR-33 respectively promoted and inhibited the differentiation of ADSCs to SCs. MiR-33 could negatively regulate P75 and GDNF expression. ICA II exerted promotion effects on differentiation of ADSCs to SCs via regulating miR-33. GDNF was identified to be a target of miR-33. MiR-33 overexpression abrogated the stimulatory effect of ICA II on ADSCs' differentiation, which was blocked by GDNF overexpression. treated with ICA II recovered the erectile function of BCNI model rats through regulation of miR-33.
CONCLUSION
ICA II contributed to the differentiation of ADSCs to SCs viamiR-33/GDNF axis, contributing to the recovery of erectile function in BCNI rats.
背景
脂肪来源的干细胞（ADSCs）具有分化为神经元样细胞的特性，这可能为主要由海绵体神经损伤引起的勃起功能障碍（ED）的修复提供新的思路。已经报道淫羊藿次苷 II（ICA II）通过刺激 ADSCs 向施万细胞（SCs）分化在调节勃起功能中发挥关键作用。然而，ICA II 在 ED 中的功能和分子机制仍有待进一步阐明。
方法
通过 qRT-PCR 检测 S100、P75、GDNF 和 miR-33 的表达。通过 Western blot 测定相对蛋白表达。通过细胞计数试剂盒-8（CCK-8）测定细胞活力。通过生物信息学、荧光素酶报告和 RNA 免疫沉淀（RIP）测定验证 miR-33 与 GDNF 之间的相互作用。通过检测海绵体内压（ICP）、ICP 与平均动脉压（MAP）的比值以及 nNOS 表达来评估双侧海绵体神经损伤（BCNI）SD 大鼠的勃起功能。
结果
ICA II 和 miR-33 分别促进和抑制 ADSCs 向SCs 的分化。miR-33 可以负调控 P75 和 GDNF 的表达。ICA II 通过调节 miR-33 对 ADSCs 向SCs 的分化发挥促进作用。GDNF 被鉴定为 miR-33 的靶基因。miR-33 过表达阻断了 ICA II 对 ADSCs 分化的刺激作用，而 GDNF 过表达则阻断了这一作用。用 ICA II 处理可通过调节 miR-33 恢复 BCNI 模型大鼠的勃起功能。
结论
ICA II 通过 miR-33/GDNF 轴促进 ADSCs 向SCs 的分化，有助于恢复 BCNI 大鼠的勃起功能。
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