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诱导多能干细胞分泌液(iPSC-cm)处理博来霉素损伤的大鼠肺后间质巨噬细胞的基因网络分析。

Gene Network Analysis of Interstitial Macrophages After Treatment with Induced Pluripotent Stem Cells Secretome (iPSC-cm) in the Bleomycin Injured Rat Lung.

机构信息

Department of Pulmonary Medicine, University Hospital Bern, 3010, Bern, Switzerland.

Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.

出版信息

Stem Cell Rev Rep. 2018 Jun;14(3):412-424. doi: 10.1007/s12015-017-9790-9.

DOI:10.1007/s12015-017-9790-9
PMID:29256173
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5960485/
Abstract

Idiopathic pulmonary fibrosis (IPF) is a complex disease involving various cell types. Macrophages are essential in maintenance of physiological homeostasis, wound repair and fibrosis in the lung. Macrophages play a crucial role in repair and remodeling by altering their phenotype and secretory pattern in response to injury. The secretome of induced pluripotent stem cells (iPSC-cm) attenuates injury and fibrosis in bleomycin injured rat lungs. In the current study, we evaluate the effect of iPSC-cm on gene expression and phenotype of interstitial macrophage in bleomycin injured rat lungs in vivo. iPSC-cm was intratracheally instilled 7 days after bleomycin induced lung injury and assessed 7 days later and single cell isolation was performed. Macrophages were FACS sorted and microarray analysis was performed. We characterized changes in the rat lung interstitial macrophages using transcriptional profiling. iPSC-cm reduced the total collagen content of the lung and reduced different macrophage populations. Gene set enrichment analysis revealed involvement of three essential pathways (a) immune modulation, (b) branching morphogenesis and (c) canonical Wnt signaling. This study demonstrates that iPSC-cm reduces fibrosis in bleomycin injured rat lung by partially altering the macrophages and regulating their gene expression.

摘要

特发性肺纤维化(IPF)是一种涉及多种细胞类型的复杂疾病。巨噬细胞在维持肺的生理稳态、伤口修复和纤维化中起着至关重要的作用。巨噬细胞通过改变其表型和分泌模式来应对损伤,在修复和重塑中发挥着关键作用。诱导多能干细胞(iPSC-cm)的分泌组可减轻博来霉素损伤的大鼠肺中的损伤和纤维化。在本研究中,我们评估了 iPSC-cm 对博来霉素诱导的大鼠肺损伤后体内间质巨噬细胞基因表达和表型的影响。在博来霉素诱导的肺损伤后 7 天,通过气管内滴注 iPSC-cm,并在 7 天后进行评估并进行单细胞分离。通过 FACS 分选巨噬细胞并进行微阵列分析。我们使用转录谱特征来描述大鼠肺间质巨噬细胞的变化。iPSC-cm 降低了肺的总胶原蛋白含量,并减少了不同的巨噬细胞群体。基因集富集分析显示了三个重要途径(a)免疫调节、(b)分支形态发生和(c)经典 Wnt 信号通路的参与。这项研究表明,iPSC-cm 通过部分改变巨噬细胞并调节其基因表达来减少博来霉素损伤的大鼠肺中的纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ff/5960485/8d4f56bd5e9f/12015_2017_9790_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ff/5960485/e6328e3caca8/12015_2017_9790_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ff/5960485/715e9fdc1cda/12015_2017_9790_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00ff/5960485/8d4f56bd5e9f/12015_2017_9790_Fig10_HTML.jpg

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