miR-21-KO Alleviates Alveolar Structural Remodeling and Inflammatory Signaling in Acute Lung Injury
miR-21-KO Alleviates Alveolar Structural Remodeling and Inflammatory Signaling in Acute Lung Injury
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DOI：
10.3390/ijms21030822
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发表时间：
2020-02-01
影响因子：
5.6
通讯作者：
Brandenberger, Christina
中科院分区：
文献类型：
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作者：
Jansing, Johanna Christine;Fiedler, Jan;Brandenberger, Christina
急性肺损伤（ALI）的特征是气血屏障通透性增强、肺水肿和低氧血症。 MicroRNA-21（miR-21）被证明参与肺重塑和 ALI 的病理学，我们假设 miR-21 敲除（KO）可减少 ALI 中的损伤和重塑。通过鼻内施用盐水中的 75 μg 脂多糖 (LPS)，在 miR-21 KO 和 C57BL/6N（野生型，WT）小鼠中诱导 ALI（每组 n = 10）。对照小鼠仅接受盐水（每组 n = 7）。 24小时后，测量肺功能。然后切除肺部进行蛋白质组学、细胞因子和体视学分析，以解决炎症信号传导和结构损伤。 LPS 暴露在两种品系中均诱发 ALI，然而，只有 WT 小鼠在 LPS 处理后表现出组织阻力增加和隔膜增厚。 WT 小鼠中 LPS 暴露导致的间隔改变包括细胞外基质 (ECM) 的增加，包括胶原纤维、弹性纤维和无定形 ECM。蛋白质组学分析显示，与 WT 小鼠相比，miR-21 KO 小鼠的炎症反应受到抑制，血小板和中性粒细胞活化减少。与 miR-21 KO 小鼠相比，WT 小鼠在 ALI 中表现出更多的功能和结构变化以及炎症信号传导，证实了 miR-21 KO 减少 ALI 病理变化发展的假设。
Acute lung injury (ALI) is characterized by enhanced permeability of the air-blood barrier, pulmonary edema, and hypoxemia. MicroRNA-21 (miR-21) was shown to be involved in pulmonary remodeling and the pathology of ALI, and we hypothesized that miR-21 knock-out (KO) reduces injury and remodeling in ALI. ALI was induced in miR-21 KO and C57BL/6N (wildtype, WT) mice by an intranasal administration of 75 mu g lipopolysaccharide (LPS) in saline (n = 10 per group). The control mice received saline alone (n = 7 per group). After 24 h, lung function was measured. The lungs were then excised for proteomics, cytokine, and stereological analysis to address inflammatory signaling and structural damage. LPS exposure induced ALI in both strains, however, only WT mice showed increased tissue resistance and septal thickening upon LPS treatment. Septal alterations due to LPS exposure in WT mice consisted of an increase in extracellular matrix (ECM), including collagen fibrils, elastic fibers, and amorphous ECM. Proteomics analysis revealed that the inflammatory response was dampened in miR-21 KO mice with reduced platelet and neutrophil activation compared with WT mice. The WT mice showed more functional and structural changes and inflammatory signaling in ALI than miR-21 KO mice, confirming the hypothesis that miR-21 KO reduces the development of pathological changes in ALI.