Department of Plastic and Aesthetic (Burn) Surgery, The Second Xiangya Hospital, Central South University, No. 139, Mid Renmin Road, Furong District, Changsha, Hunan, 410011, People's Republic of China.
Hum Cell. 2022 Sep;35(5):1375-1390. doi: 10.1007/s13577-022-00732-2. Epub 2022 Jun 25.
Exosomes (Exos) extracted from human adipose mesenchymal stromal/stem cells (hAD-MSCs) have been reported as therapeutic tools for tissue repair, but how they regulate angiogenesis of endothelial cells remains unknown. In this study, hAD-MSCs were isolated, and early growth response factor-1, Smooth muscle and endothelial cell enriched migration/differentiation-associated long-noncoding RNA (lncRNA-SENCR), and vascular endothelial growth factor-A (VEGF-A) overexpression or knockdown was achieved. Exos extracted from hAD-MSCs (hADSC-Exos) were co-cultured with human umbilical vein endothelial cells (HUVECs) to detect the effects of EGR-1, lncRNA-SENCR, and VEGF-A on angiogenesis and the relationships between EGR-1, lncRNA-SENCR, Dyskerin pseudouridine synthase 1 (DKC1), and VEGF-A. An in vivo experiment verified the effect of hADSC-Exos on the wound healing process. hADSC-Exos substantially promoted the proliferation, migration, and angiogenesis of HUVECs, which could be reversed by short-hairpin RNA SENCR (shSENCR) transfection. hADSC-Exos had elevated expression of EGR-1, which bound to the lncRNA-SENCR promoter. The suppressive effect of Exo-shEGR1 on HUVECs was counteracted by SENCR overexpression. LncRNA-SENCR was shown to interact with DKC1. Overexpression of DKC1 or lncRNA-SENCR maintained stable VEGF-A expression. Overexpression of VEGF-A reversed the suppressive effect of shSENCR on HUVECs. Consistent results were obtained in mice in vivo. Overall, hADSC-Exo EGR-1 upregulates lncRNA-SENCR expression to activate the DKC1/VEGF-A axis, facilitating the wound-healing process by increasing angiogenesis.
从人脂肪间充质基质/干细胞（hAD-MSCs）中提取的外泌体（Exos）已被报道为组织修复的治疗工具，但它们如何调节内皮细胞的血管生成仍不清楚。在这项研究中，分离了 hAD-MSCs，并实现了早期生长反应因子-1、富含平滑肌和内皮细胞的迁移/分化相关长非编码 RNA（lncRNA-SENCR）和血管内皮生长因子-A（VEGF-A）的过表达或敲低。将 hAD-MSCs 提取的外泌体（hADSC-Exos）与人脐静脉内皮细胞（HUVEC）共培养，以检测 EGR-1、lncRNA-SENCR 和 VEGF-A 对血管生成的影响，以及 EGR-1、lncRNA-SENCR、DKC1 和 VEGF-A 之间的关系。体内实验验证了 hADSC-Exos 对伤口愈合过程的影响。hADSC-Exos 显著促进了 HUVEC 的增殖、迁移和血管生成，这可以通过短发夹 RNA SENCR（shSENCR）转染来逆转。hADSC-Exos 上调了 EGR-1 的表达，EGR-1 与 lncRNA-SENCR 启动子结合。Exo-shEGR1 对 HUVEC 的抑制作用被 SENCR 过表达抵消。lncRNA-SENCR 被证明与 DKC1 相互作用。DKC1 或 lncRNA-SENCR 的过表达维持了 VEGF-A 的稳定表达。VEGF-A 的过表达逆转了 shSENCR 对 HUVEC 的抑制作用。在体内小鼠中也得到了一致的结果。总体而言，hADSC-Exo EGR-1 上调 lncRNA-SENCR 的表达，激活 DKC1/VEGF-A 轴，通过增加血管生成促进伤口愈合过程。
