Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p.
Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p.
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巨噬细胞来源的外泌体通过递送抗纤维化miR-142- 3 p减轻气道上皮细胞中的纤维化
DOI：
10.1136/thoraxjnl-2019-214077
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发表时间：
2020-10
期刊：
影响因子：
10
通讯作者：
Njock MS
中科院分区：
文献类型：
--
作者：
Guiot J;Cambier M;Boeckx A;Henket M;Nivelles O;Gester F;Louis E;Malaise M;Dequiedt F;Louis R;Struman I;Njock MS
特发性肺纤维化（IPF）是一种病因和治疗不明的进行性纤维化间质性肺病。最近的研究报告了IPF背景下外来体microRNA（miR）的失调。然而，IPF相关外泌体miR对肺纤维化进展的影响尚不清楚。两个独立的队列在列日大学的门诊护理综合诊所入组。从19名IPF患者和23名健康受试者（HS）（队列1）获得来自痰的外泌体，并且从来自14名IPF患者和14名HS（队列2）的血浆获得外泌体。通过定量逆转录-PCR进行外泌体miR表达。通过在人肺泡上皮细胞和肺成纤维细胞中转染miR模拟物来体外评估外泌体miR的功能作用。外泌体miR分析显示，miR-142- 3 p在IPF患者的痰液和血浆中显著上调（分别为8.06倍，p<0.0001; 1.64倍，p=0.008）。相关性分析揭示了外泌体miR-142- 3 p与IPF患者痰液中巨噬细胞百分比之间的正相关性（r=0.576，p=0.012），表明外泌体miR-142- 3 p上调的巨噬细胞来源。miR-142- 3 p在肺泡上皮细胞和肺成纤维细胞中的过表达能够降低转化生长因子β受体1（TGFβ-R1）和促纤维化基因的表达。此外，从巨噬细胞分离的外泌体呈现抗纤维化特性，部分归因于靶细胞中miR-142- 3 p转移对TGFβ-R1的抑制。我们的研究结果表明，巨噬细胞来源的外泌体可以通过将抗纤维化miR-142-3 p递送至肺泡上皮细胞和肺成纤维细胞来对抗肺纤维化进展。
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in the IPF context. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown. Two independent cohorts were enrolled at the ambulatory care polyclinic of Liège University. Exosomes from sputum were obtained from 19 patients with IPF and 23 healthy subjects (HSs) (cohort 1), and the ones from plasma derived from 14 patients with IPF and 14 HSs (cohort 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts. Exosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of patients with IPF (8.06-fold, p<0.0001; 1.64 fold, p=0.008, respectively). Correlation analysis revealed a positive association between exosomal miR-142-3p and the percentage of macrophages from sputum of patients with IPF (r=0.576, p=0.012), suggesting macrophage origin of exosomal miR-142-3p upregulation. The overexpression of miR-142-3p in alveolar epithelial cells and lung fibroblasts was able to reduce the expression of transforming growth factor β receptor 1 (TGFβ-R1) and profibrotic genes. Furthermore, exosomes isolated from macrophages present antifibrotic properties due in part to the repression of TGFβ-R1 by miR-142-3p transfer in target cells. Our results suggest that macrophage-derived exosomes may fight against pulmonary fibrosis progression via the delivery of antifibrotic miR-142–3 p to alveolar epithelial cells and lung fibroblasts.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
5.7
作者：
Guiot J;Struman I;Chavez V;Henket M;Herzog M;Scoubeau K;Hardat N;Bondue B;Corhay JL;Moermans C;Louis R
通讯作者：
Louis R
影响因子：
33.5
作者：
Lu X;Wei Y;Liu F
通讯作者：
Liu F
影响因子：
11.1
作者：
Cheng, Henry S.;Sivachandran, Nirojini;Lau, Andrew;Boudreau, Emilie;Zhao, Jimmy L.;Baltimore, David;Delgado-Olguin, Paul;Cybulsky, Myron I.;Fish, Jason E.
通讯作者：
Fish, Jason E.
影响因子：
4.3
作者：
Jin, Chang'e;Xiao, Liang;Ren, Shuhua
通讯作者：
Ren, Shuhua