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Exosomes from adipose-derived stem cells protect against high glucose-induced erectile dysfunction by delivery of corin in a streptozotocin-induced diabetic rat model.
Regenerative Therapy ( IF 4.3 ) Pub Date : 2020-05-15 , DOI: 10.1016/j.reth.2020.03.002
Jian Wang 1 , Yuanyuan Mi 1 , Sheng Wu 1 , Xiaoming You 1 , Yi Huang 1 , Jin Zhu 2 , Lijie Zhu 1
Affiliation  

Introduction

Increasing study have found that stem cell transplantation have a therapeutical effect to diabetes mellitus (DM)-induced erectile dysfunction (ED). So, the aim of this study was to evaluate the beneficial effect of corin from adipose-derived stem cells (ADSCs) on DM-induced ED.

Methods

Exosomes were isolated from ADSCs (ADSC-EXOs) or from ADSCs in which corin gene expression was silenced by siRNA (siCorin). For in vivo studies, rats with streptozotocin-induced DM were intravenously injected with ADSC-EXOs or siCorin-ADSC-EXOs. Two weeks later, intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured to assess erectile function, and penile tissues were harvested for further evaluation of levels of inflammatory factors and expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and neuronal nitric oxide synthase (nNOS). We also evaluated the recovery of neurovascular function in penile tissues by immunofluorescence analysis.

Results

The results showed that ADSC-EXOs restored erectile function in diabetic rats, as determined by the ICP/MAP ratio. Exosomes from ADSCs also promoted neurovascular function and suppressed expression of inflammatory factors. In contrast, the decreased content of corin in exosomes after silencing corin in ADSCs reduced the therapeutic effect of exosomes on ED.

Conclusion

These findings demonstrated the therapeutic mechanism underlying the use of ADSC-EXOs for treating ED and the beneficial effect of corin.



中文翻译:

来自脂肪干细胞的外泌体通过在链脲佐菌素诱导的糖尿病大鼠模型中递送 corin 来防止高葡萄糖诱导的勃起功能障碍。

介绍

越来越多的研究发现,干细胞移植对糖尿病(DM)引起的勃起功能障碍(ED)具有治疗作用。因此,本研究的目的是评估来自脂肪干细胞 (ADSC) 的 corin 对 DM 诱导的 ED 的有益作用。

方法

外泌体从 ADSC (ADSC-EXO) 或从其中 corin 基因表达被 siRNA (siCorin) 沉默的 ADSC 中分离出来。对于体内研究,链脲佐菌素诱导的 DM 大鼠被静脉注射 ADSC-EXO 或 siCorin-ADSC-EXO。两周后,测量海绵体内压(ICP)和平均动脉压(MAP)以评估勃起功能,并收集阴茎组织用于进一步评估炎症因子水平和心钠素(ANP)、脑钠肽的表达。 BNP) 和神经元一氧化氮合酶 (nNOS)。我们还通过免疫荧光分析评估了阴茎组织中神经血管功能的恢复。

结果

结果表明,ADSC-EXOs 恢复了糖尿病大鼠的勃起功能,这由 ICP/MAP 比率确定。ADSCs 的外泌体还促进神经血管功能并抑制炎症因子的表达。相反,沉默ADSCs中corin后外泌体中corin含量的降低降低了外泌体对ED的治疗效果。

结论

这些发现证明了使用 ADSC-EXO 治疗 ED 的治疗机制和 corin 的有益作用。

更新日期:2020-05-15
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