Dimethyl Itaconate‐Loaded Nanofibers Rewrite Macrophage Polarization, Reduce Inflammation, and Enhance Repair of Myocardic Infarction,Small

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Dimethyl Itaconate‐Loaded Nanofibers Rewrite Macrophage Polarization, Reduce Inflammation, and Enhance Repair of Myocardic Infarction
Small ( IF 13.0 ) Pub Date : 2021-03-14 , DOI: 10.1002/smll.202006992
Jayachandra Reddy Nakkala _{1,

2} , Yuejun Yao ₁ , Zihe Zhai ₁ , Yiyuan Duan _{1,

2} , Deteng Zhang _{1,

2} , Zhengwei Mao ₁ , Linrong Lu ₂ , Changyou Gao _{1,

2}

Affiliation

Cellular metabolism plays a major role in the regulation of inflammation. The inflammatory macrophages undergo a wide‐range of metabolic rewriting due to the production of significant amount of itaconate metabolite from cis‐aconitate in the tricarboxylic acid cycle. This itaconate molecule has been recently described as a promising immunoregulator. However, its function and mode of action on macrophages and tissue repair and regeneration are yet unclear. Herein, the itaconate‐derivative dimethyl itaconate (DMI) suppresses the IL‐23/IL‐17 inflammatory axis‐associated genes and promotes antioxidant nuclear factor erythroid 2‐related factor 2 target genes. The poly‐ε‐caprolactone (PCL)/DMI nanofibers implanted in mice initially maintain inflammation by suppressing anti‐inflammatory activity and particular inflammation, while at later stage promotes anti‐inflammatory activity for an appropriate tissue repair. Furthermore, the PCL/DMI nanofiber patches show an excellent myocardial protection by reducing infarct area and improving ventricular function via time‐dependent regulation of myocardium‐associated genes. This study unveils potential DMI macrophage modulatory functions in tissue microenvironment and macrophages rewriting for proper tissue repair.

中文翻译：

衣康酸二甲酯负载的纳米纤维可重写巨噬细胞极化，减少炎症并增强心肌梗死的修复

细胞代谢在炎症调节中起主要作用。由于三羧酸循环中顺式衣康酸酯产生大量衣康酸酯代谢产物，因此炎症巨噬细胞经历了广泛的代谢改写。最近已将该衣康酸酯分子描述为有前途的免疫调节剂。然而，其对巨噬细胞以及组织修复和再生的功能和作用方式尚不清楚。在本文中，衣康酸酯衍生物衣康酸二甲酯（DMI）抑制了IL-23 / IL-17炎症轴相关基因，并促进了抗氧化剂核因子红系2相关因子2靶基因。植入小鼠体内的聚ε-己内酯（PCL）/ DMI纳米纤维最初通过抑制抗炎活性和特定的炎症来维持炎症，而在后期则促进抗炎活性，以进行适当的组织修复。此外，PCL / DMI纳米纤维贴片通过减少心肌梗死面积并通过对心肌相关基因的时间依赖性调节来改善心室功能，从而表现出出色的心肌保护作用。这项研究揭示了组织微环境中潜在的DMI巨噬细胞调节功能和巨噬细胞重写，以进行适当的组织修复。

更新日期：2021-04-27

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