Outsourcing Invasion, a Novel Function for Extracellular Vesicles in the Lung.
Outsourcing Invasion, a Novel Function for Extracellular Vesicles in the Lung.
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外包入侵，肺细胞外囊泡的一种新功能。
DOI：
10.1165/rcmb.2018-0345ed
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发表时间：
2019
影响因子：
6.4
通讯作者：
Hagood,JamesS
中科院分区：
文献类型：
--
作者：
Shentu,Tzu-Pin;Hagood,JamesS
Activated fibroblasts in fibrotic lungs demonstrate increased adhesion, chemotaxis, matrix metalloproteinase secretion, and collagen deposition, comprising a matrix-invasive phenotype (1). However, the molecular mechanisms that drive this phenotype are not well understood. Signals from the matrix itself, be they biophysical through mechanosensing (2) or via changes in extracellular matrix (ECM) composition, seem to regulate the aberrant invasive phenotype (3). Cell-to-cell communication via the secretome, however, is increasingly appreciated as a driver of pathologic fibroblast differentiation. A recent study demonstrated that WNT-5a on extracellular vesicles (EVs) secreted from lung fibroblasts contributes to progression of lung fibrogenesis (4), establishing a role for EVs in pulmonary fibrosis through cell–cell communication. EVs, which can deliver genetic information (largely noncoding RNA), bioactive lipids, and proteins, are increasingly appreciated as important messengers conveying phenotype-altering signals between cells (5, 6). In this issue of the Journal (pp. 279–288), Chanda and colleagues (7) bring paracrine signaling and matrix signaling together by demonstrating that EV-associated fibronectin (FN) changes fibroblast phenotype by engaging cellular integrin a5b1 signaling. Chanda and colleagues undertook complementary approaches to assess the central hypothesis that surface expression of FN on EVs contributes to fibroblast migration and invasion. The authors used a cellular model of replicative senescence in IMR-90 fibroblasts to begin their studies. Cellular senescence is an important paradigm in pulmonary fibrosis that is associated with changes in the secretome that drive remodeling (8). Fibroblasts with high population-doubling levels (45 to 55), abbreviated “HPDL,” represented senescence in this study, and they were compared with low population doubling (LPDL;, 30). This simple in vitro model of senescence was compared in cultured normal versus idiopathic pulmonary fibrosis fibroblasts and also with fibroblasts treated with transforming growth factor-b1. Although the latter groups had increased EV production, HPDL cells had the highest levels of EV production by an order of magnitude, suggesting that EV secretion was strongly correlated with the degree of cellular senescence. The EVs in these different conditions were of a similar size range. Proteomics revealed abundant ECM proteins, particularly FN, in the EV; comparison of senescence-associated versus normal EV proteomes demonstrated enrichment for cellular adhesion and ECM remodeling. Interestingly, the majority of the transforming growth factor-b1–induced and HPDL-derived EVs were located not in the conditioned media but in the ECM. Next, Chanda and colleagues considered whether EVs could alter fibroblast phenotype, specifically whether EVs could impact fibroblast invasion. They found that EVs added to Matrigel amplified the invasive phenotype of LPDL nonsenescent fibroblasts. This invasive phenotype induction was found to be dependent on FN on vesicles and could also be induced by direct incubation of EV with fibroblasts and subsequent removal.
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肌醇三磷酸诱导透化瑞士小鼠 3T3 细胞钙释放的特异性。
影响因子：
4.1
作者：
R. Irvine;K. Brown;M. Berridge
通讯作者：
M. Berridge
完整仓鼠胰岛素瘤细胞中 Ca2 依赖性蛋白磷酸化和胰岛素释放。
DOI：
--
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Schubart,UK;Fleischer,N;Erlichman,J
通讯作者：
Erlichman,J
DOI：
10.1073/pnas.76.4.1838
发表时间：
1979-01-01
影响因子：
11.1
作者：
DELORENZO, RJ;FREEDMAN, SD;MAURER, SC
通讯作者：
MAURER, SC
DOI：
10.1097/00132586-197712000-00007
发表时间：
1977
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
K. Morgan;S. Bryant
通讯作者：
S. Bryant
DOI：
--
发表时间：
1980-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Kishimoto;Y. Takai;T. Mori;U. Kikkawa;Y. Nishizuka
通讯作者：
A. Kishimoto;Y. Takai;T. Mori;U. Kikkawa;Y. Nishizuka