MG53 Protects hUC-MSCs against Inflammatory Damage and Synergistically Enhances Their Efficacy in Neuroinflammation Injured Brain through Inhibiting NLRP3/Caspase-1/IL-1β Axis.,ACS Chemical Neuroscience

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MG53 Protects hUC-MSCs against Inflammatory Damage and Synergistically Enhances Their Efficacy in Neuroinflammation Injured Brain through Inhibiting NLRP3/Caspase-1/IL-1β Axis.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-07-30 , DOI: 10.1021/acschemneuro.0c00268
Shanshan Ma _{1,

2} , Yaping Wang ₁ , Xinkui Zhou ₁ , Zhe Li ₁ , Zhenkun Zhang ₁ , Yingying Wang ₁ , Tuanjie Huang ₁ , Yanting Zhang ₁ , Jijing Shi ₃ , Fangxia Guan _{1,

2}

Affiliation

The inflammatory microenvironment in a lesion is not conducive to the survival of stem cells. Improving the inflammatory microenvironment may be an alternative strategy to enhance the efficacy of stem cells. We evaluated the therapeutic effect and molecular mechanism of mitsugumin53 (MG53) on lipopolysaccharide (LPS)-induced damage in human umbilical cord mesenchymal stem cells (hUC-MSCs) and in C57/BL6 mice. MG53 significantly promoted the proliferation and migration of hUC-MSCs, protected hUC-MSCs against LPS-induced apoptosis and mitochondrial dysfunction, and reversed LPS-induced inflammatory cytokine release. Furthermore, MG53 combined with hUC-MSCs transplantation improved LPS-induced memory impairment and activated neurogenesis by promoting the migration of hUC-MSCs and enhancing βIII-tubulin and doublecortin (DCX) expression. MG53 protein combined with hUC-MSCs improved the M1/M2 phenotype polarization of microglia accompanied by lower inducible nitric oxide synthase (iNOS) expression and higher arginase 1 (ARG1) expression. MG53 significantly suppressed the expression of tumor necrosis factor α (TNF-α), Toll-like receptor 4 (TLR4), nucleotide oligomerization domain-like receptor protein 3 (NLRP3), cleaved-caspase-1, and interleukin (IL)-1β to alleviate LPS-induced neuroinflammation on hUC-MSCs and C57/BL6 mice. In conclusion, our results indicated that MG53 could protect hUC-MSCs against LPS-induced inflammatory damage and facilitate their efficacy in LPS-treated C57/BL6 mice partly by inhibiting the NLRP3/caspase-1/IL-1β axis.

中文翻译：

MG53 通过抑制 NLRP3/Caspase-1/IL-1β 轴保护 hUC-MSCs 免受炎症损伤并协同增强其在神经炎症损伤脑中的功效。

病灶内的炎症微环境不利于干细胞的存活。改善炎症微环境可能是增强干细胞功效的一种替代策略。我们评估了 mitsugumin53 (MG53) 对人脐带间充质干细胞 (hUC-MSCs) 和 C57/BL6 小鼠中脂多糖 (LPS) 诱导的损伤的治疗效果和分子机制。MG53显着促进hUC-MSCs的增殖和迁移，保护hUC-MSCs免受LPS诱导的细胞凋亡和线粒体功能障碍，并逆转LPS诱导的炎性细胞因子释放。此外，MG53 联合 hUC-MSCs 移植通过促进 hUC-MSCs 的迁移和增强 βIII-微管蛋白和双皮质素 (DCX) 的表达来改善 LPS 诱导的记忆障碍和激活神经发生。MG53 蛋白联合 hUC-MSCs 改善了小胶质细胞的 M1/M2 表型极化，同时降低了诱导型一氧化氮合酶 (iNOS) 的表达和更高的精氨酸酶 1 (ARG1) 表达。MG53 显着抑制肿瘤坏死因子 α (TNF-α)、Toll 样受体 4 (TLR4)、核苷酸寡聚结构域样受体蛋白 3 (NLRP3)、cleaved-caspase-1 和白细胞介素 (IL)-1β 的表达减轻 LPS 诱导的 hUC-MSCs 和 C57/BL6 小鼠的神经炎症。总之，我们的结果表明，MG53 可以保护 hUC-MSCs 免受 LPS 诱导的炎症损伤，并通过抑制 NLRP3/caspase-1/IL-1β 轴促进其在 LPS 处理的 C57/BL6 小鼠中的功效。

更新日期：2020-09-02

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