环鞘氨醇-1-磷酸引发的间充质干细胞改善lps诱导的小鼠急性肺损伤。

IF 2.5 4区 医学 Q3 CELL & TISSUE ENGINEERING
Youngheon Park, Jimin Jang, Jooyeon Lee, Hyosin Baek, Jaehyun Park, Sang-Ryul Cha, Se Bi Lee, Sunghun Na, Jae-Woo Kwon, Seok-Ho Hong, Se-Ran Yang
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引用次数: 1

摘要

背景与目的:o -环鞘氨醇-1-磷酸(cP1P)是一种具有类似鞘氨醇-1-磷酸(S1P)结构的人工合成化合物。已知S1P通过海马信号促进细胞迁移、侵袭、增殖和抗凋亡。然而,S1P介导的细胞分子机制仍然存在于肺中。急性肺损伤(ALI)及其严重形式的急性呼吸窘迫综合征(ARDS)的特征是免疫反应过度、血管通透性增加、肺泡-腹膜屏障塌陷和水肿。在这项研究中,我们确定了cP1P引发的人真皮源性间充质干细胞(hdMSCs)是否能改善ALI小鼠的肺损伤及其治疗途径。方法和结果:cP1P处理显著促进MSC迁移和侵袭能力。在细胞因子阵列中,cP1P引发的hdMSCs (hdMSCcP1P)中血管相关因子的分泌增加,cP1P处理诱导了Lats的抑制,同时增加了Yap的磷酸化。接下来,我们确定hdMSCcP1P是否会减少LPS暴露小鼠的炎症反应。hdMSCcP1P进一步降低了巨噬细胞和中性粒细胞的浸润,TNF-α、IL-1β和IL-6的释放比naïve hdMSC治疗减少。此外,MSCcP1P处理小鼠肺中STAT1的磷酸化和iNOS的表达显著降低。结论:综上所述,这些数据表明,cP1P治疗增强了hdMSC在Hippo信号调控中的迁移,MSCcP1P为ALI/ARDS治疗提供了治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice.

Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice.

Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice.

Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice.

Background and objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice.

Methods and results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice.

Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.

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来源期刊
International journal of stem cells
International journal of stem cells Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
5.10
自引率
4.30%
发文量
38
期刊介绍: International Journal of Stem Cells (Int J Stem Cells), a peer-reviewed open access journal, principally aims to provide a forum for investigators in the field of stem cell biology to present their research findings and share their visions and opinions. Int J Stem Cells covers all aspects of stem cell biology including basic, clinical and translational research on genetics, biochemistry, and physiology of various types of stem cells including embryonic, adult and induced stem cells. Reports on epigenetics, genomics, proteomics, metabolomics of stem cells are welcome as well. Int J Stem Cells also publishes review articles, technical reports and treatise on ethical issues.
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