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骨髓来源的淋巴细胞中表达的 miR-155 通过 Ang-2-Tie-2 通路促进脂多糖诱导的急性肺损伤。

MiR-155 expressed in bone marrow-derived lymphocytes promoted lipopolysaccharide-induced acute lung injury through Ang-2-Tie-2 pathway.

机构信息

Department of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang, 110004, China.

School of Fundamental Sciences, China Medical University, Shenyang, 110122, China.

出版信息

Biochem Biophys Res Commun. 2019 Mar 12;510(3):352-357. doi: 10.1016/j.bbrc.2019.01.079. Epub 2019 Feb 1.

Abstract

Acute lung injury (ALI) is a type of diffuse lung inflammation with a high mortality rate. Studies show that miR-155 plays an important role in inflammation. Here, we investigated the role of miR-155 in lipopolysaccharide (LPS)-induced ALI. The mice with bone marrow transplantation between MiR-155 knockout and wild-type were used as animal models of LPS-induced sepsis. In response to LPS injection, ALI was less severe in miR-155 knockout mice than in wild-type mice, and mainly manifested as reduced pulmonary vascular leakage, pulmonary edema, and neutrophil infiltration. The expression levels of Ang-2 and apoptosis-associated caspases-3 and -9, as well as myosin light chain (MLC) phosphorylation in the lungs were also decreased. A bone marrow transplantation experiment showed that miR-155 expressed in bone marrow-derived lymphocytes rather than lung parenchymal lymphocytes promoted inflammation. Findings suggest that miR-155 expressed in bone marrow-derived lymphocytes promoted LPS-induced ALI through the modulation of the Ang-2-Tie-2 pathway.

摘要

急性肺损伤(ALI)是一种弥漫性肺炎症,死亡率较高。研究表明,miR-155 在炎症中发挥重要作用。在这里,我们研究了 miR-155 在脂多糖(LPS)诱导的 ALI 中的作用。将 miR-155 敲除和野生型之间的骨髓移植小鼠用作 LPS 诱导的脓毒症动物模型。对 LPS 注射的反应中,miR-155 敲除小鼠的 ALI 比野生型小鼠轻,主要表现为肺血管渗漏、肺水肿和中性粒细胞浸润减少。肺中的 Ang-2 和凋亡相关的半胱天冬酶-3 和 -9 表达水平以及肌球蛋白轻链(MLC)磷酸化也降低。骨髓移植实验表明,骨髓来源的淋巴细胞中表达的 miR-155 而不是肺实质淋巴细胞促进了炎症。研究结果表明,骨髓来源的淋巴细胞中表达的 miR-155 通过调节 Ang-2-Tie-2 通路促进 LPS 诱导的 ALI。

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