Shen Ye-Zhou, Yang Guang-Ping, Ma Qi-Min, Wang Yu-Song, Wang Xin
Department of Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, China.
Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
World J Stem Cells. 2025 Mar 26;17(3):100079. doi: 10.4252/wjsc.v17.i3.100079.
Acute lung injury (ALI) is a fatal and heterogeneous disease. While bone marrow mesenchymal stem cells (BMSCs) have shown promise in ALI repair, their efficacy is compromised by a high apoptotic percentage. Preliminary findings have indicated that long noncoding RNA (lncRNA)-ENST expression is markedly downregulated in MSCs under ischemic and hypoxic conditions, establishing a rationale for exploration.
To elucidate the role of lncRNA-ENST00000517482 (lncRNA-ENST) in modulating MSC apoptosis.
Founded on ALI in BEAS-2B cells with lipopolysaccharide, this study employed a transwell co-culture system to study BMSC tropism. BMSCs were genetically modified to overexpress or knockdown lncRNA-ENST. After analyzing the effects on autophagy, apoptosis and cell viability, the lncRNA-ENST/miR-539/c-MYC interaction was confirmed by dual-luciferase assays.
These findings have revealed a strong correlation between lncRNA-ENST levels and the apoptotic and autophagic status of BMSCs. On the one hand, the over-expression of lncRNA-ENST, as determined by Cell Counting Kit-8 assays, increased the expression of autophagy markers LC3B, ATG7, and ATG5. On the other hand, it reduced apoptosis and boosted BMSC viability. In co-cultures with BEAS-2B cells, lncRNA-ENST overexpression also improved cell vitality. Additionally, by downregulating miR-539 and upregulating c-MYC, lncRNA-ENST was found to influence mitochondrial membrane potential, enhance BMSC autophagy, mitigate apoptosis and lower the secretion of pro-inflammatory cytokines interleukin-6 and interleukin-1β. Collectively, within the framework, these results have highlighted the therapeutic potential of BMSCs in ALI and the pivotal regulatory role of lncRNA-ENST in miR-539 and apoptosis in lipopolysaccharide-stimulated BEAS-2B cells.
Our results show that enhanced lncRNA ENST expression can promote BMSC proliferation and viability by modulating the miR-539/c-MYC axis, reduce apoptosis and induce autophagy, which has suggested its therapeutic potential in the treatment of ALI.
急性肺损伤（ALI）是一种致命的异质性疾病。虽然骨髓间充质干细胞（BMSCs）在ALI修复中显示出前景，但其疗效因高凋亡率而受到影响。初步研究结果表明，长链非编码RNA（lncRNA）-ENST在缺血缺氧条件下的间充质干细胞中表达明显下调，这为探索其作用提供了理论依据。
阐明长链非编码RNA-ENST00000517482（lncRNA-ENST）在调节间充质干细胞凋亡中的作用。
基于脂多糖诱导BEAS-2B细胞发生ALI，本研究采用Transwell共培养系统研究骨髓间充质干细胞的趋化性。对骨髓间充质干细胞进行基因改造以过表达或敲低lncRNA-ENST。在分析其对自噬、凋亡和细胞活力的影响后，通过双荧光素酶测定法证实了lncRNA-ENST/miR-539/c-MYC相互作用。
这些发现揭示了lncRNA-ENST水平与骨髓间充质干细胞的凋亡和自噬状态之间存在密切关联。一方面，通过细胞计数试剂盒-8检测确定，lncRNA-ENST的过表达增加了自噬标志物LC3B、ATG7和ATG5的表达。另一方面，它减少了细胞凋亡并提高了骨髓间充质干细胞的活力。在与BEAS-2B细胞的共培养中，lncRNA-ENST的过表达也提高了细胞活力。此外，发现lncRNA-ENST通过下调miR-539和上调c-MYC来影响线粒体膜电位，增强骨髓间充质干细胞自噬，减轻细胞凋亡并降低促炎细胞因子白细胞介素-6和白细胞介素-1β的分泌。总体而言，在这个框架内，这些结果突出了骨髓间充质干细胞在ALI中的治疗潜力以及lncRNA-ENST在脂多糖刺激的BEAS-2B细胞中对miR-539和凋亡的关键调节作用。
我们的结果表明，增强lncRNA ENST的表达可通过调节miR-539/c-MYC轴促进骨髓间充质干细胞的增殖和活力，减少细胞凋亡并诱导自噬，这表明其在ALI治疗中的潜在治疗价值。
