Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, China.
Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
J Cell Mol Med. 2021 Oct;25(20):9796-9804. doi: 10.1111/jcmm.16927. Epub 2021 Sep 20.
This study aimed to explore the possibility of miR-423-5p modified adipose-derived stem cell (ADSCs) therapy on streptozotocin (STZ)-induced diabetes mellitus erectile dysfunction (DMED) rats. MiR-423-5p was knocked down in ADSCs. ADSCs, NC-miR-ADSCs and miR-ADSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). Normal and high glucose media were supplemented. The supernatant and HUVECs were collected for assessment of eNOS and VEGFa expression, cell proliferation, and apoptosis. HUVECs co-cultured with ADSCs or miR-ADSCs exhibited higher eNOS and VEGFa protein expression levels compared to DM groups. MiR-ADSCs enhanced HUVEC proliferation compared to the ADSCs and NC-miR-ADSCs. Lower apoptotic rates were observed when HUVECs were co-cultured with miR-ADSCs, compared to ADSCs and NC-miR-ADSCs. Fifteen male Sprague-Dawley (SD) rats aged 12 weeks were induced to develop diabetes mellitus by intraperitoneal injection with STZ, and five healthy SD rats were used as normal controls. Eight weeks after developing diabetes, the rats received ADSCs and miR-ADSCs via injection into the corpora cavernosa, whereas normal controls and DM controls were injected with saline. Erectile function and histological assessment of penile tissues were performed 8 weeks after injection. The ICP/MAP indicated that erectile function was impaired in the DM rats compared with the normal group. Injection of ADSCs and miR-ADSCs improved erectile function significantly and was associated with the overexpression of eNOS and VEGFa. MiR-423-5p knockdown in ADSCs ameliorated high glucose-mediated damage to HUVECs and improved erectile function in DM rats by inducing eNOS and VEGFa overexpression, indicating that miR-423-5p may be a potential target in the treatment of DMED.
本研究旨在探讨 miR-423-5p 修饰脂肪来源干细胞（ADSCs）治疗链脲佐菌素（STZ）诱导的糖尿病性勃起功能障碍（DMED）大鼠的可能性。miR-423-5p 在 ADSCs 中被敲低。将 ADSCs、NC-miR-ADSCs 和 miR-ADSCs 与人脐静脉内皮细胞（HUVECs）共培养。补充正常和高糖培养基。收集上清液和 HUVECs 以评估 eNOS 和 VEGFa 表达、细胞增殖和凋亡。与 DM 组相比，与 ADSCs 或 miR-ADSCs 共培养的 HUVECs 表现出更高的 eNOS 和 VEGFa 蛋白表达水平。与 ADSCs 和 NC-miR-ADSCs 相比，miR-ADSCs 增强了 HUVEC 的增殖。与 ADSCs 和 NC-miR-ADSCs 共培养时，HUVEC 的凋亡率较低。15 只 12 周龄雄性 Sprague-Dawley（SD）大鼠经腹腔注射 STZ 诱导糖尿病，5 只健康 SD 大鼠作为正常对照。糖尿病发病 8 周后，将 ADSCs 和 miR-ADSCs 注射到海绵体中，而正常对照和 DM 对照则注射生理盐水。注射 8 周后进行阴茎组织的勃起功能和组织学评估。ICP/MAP 表明，与正常组相比，DM 组的勃起功能受损。ADSCs 和 miR-ADSCs 的注射显著改善了勃起功能，与 eNOS 和 VEGFa 的过表达有关。ADSCs 中的 miR-423-5p 敲低减轻了高糖对 HUVECs 的损伤，并通过诱导 eNOS 和 VEGFa 的过表达改善了 DM 大鼠的勃起功能，表明 miR-423-5p 可能是治疗 DMED 的潜在靶点。
