Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany.
Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany.
Int J Mol Sci. 2020 Jan 27;21(3):822. doi: 10.3390/ijms21030822.
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 µg lipopolysaccharide (LPS) in saline ( = 10 per group). The control mice received saline alone ( = 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.
急性肺损伤（ALI）的特征是肺泡-毛细血管屏障通透性增加、肺水肿和低氧血症。已经证明 microRNA-21（miR-21）参与了肺重塑和 ALI 的病理学，我们假设 miR-21 敲除（KO）可减轻 ALI 中的损伤和重塑。通过向 miR-21 KO 和 C57BL/6N（野生型，WT）小鼠的鼻腔内给予 75 µg 脂多糖（LPS）在盐水中（每组 = 10 只）诱导 ALI。对照组小鼠仅接受生理盐水（每组 = 7 只）。24 小时后，测量肺功能。然后切除肺部进行蛋白质组学、细胞因子和立体学分析，以解决炎症信号和结构损伤。LPS 暴露在两种菌株中均诱导了 ALI，但只有 WT 小鼠在 LPS 处理后表现出组织阻力增加和间隔增厚。WT 小鼠中由于 LPS 暴露引起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 小鼠中的血小板和中性粒细胞激活减少，炎症反应减弱。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，证实了 miR-21 KO 可减轻 ALI 中病理性变化发展的假设。
