TGF-β1-Containing Exosomes from Injured Epithelial Cells Activate Fibroblasts to Initiate Tissue Regenerative Responses and Fibrosis
TGF-β1-Containing Exosomes from Injured Epithelial Cells Activate Fibroblasts to Initiate Tissue Regenerative Responses and Fibrosis
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DOI：
10.1681/asn.2012101031
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发表时间：
2013-03-01
影响因子：
13.6
通讯作者：
Kalluri, Raghu
中科院分区：
文献类型：
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作者：
Borges, Fernanda T.;Melo, Sonia A.;Kalluri, Raghu
缺氧与组织损伤和纤维化有关，但其在成纤维细胞活化和组织修复/再生中的功能作用尚不清楚。使用肾损伤作为模型系统，我们证明了损伤的上皮细胞产生增加数量的具有定义的遗传信息的外泌体以激活成纤维细胞。由损伤的上皮细胞释放的外泌子促进成纤维细胞中的增殖、α-平滑肌肌动蛋白表达、F-肌动蛋白表达和I型胶原蛋白产生。成纤维细胞活化依赖于递送TGF-β 1 mRNA的外泌体以及其他尚未鉴定的部分。这项研究表明，TGF-β 1 mRNA的外泌体运输构成了一个快速的反应，启动组织修复/再生反应和激活成纤维细胞时，居民的实质损伤。这些结果还为外泌体靶向治疗控制组织纤维化的潜在效用提供了信息。J Am Soc Nephrol 24：385-392，2013. doi：10.1681/ASN. 2012101031
Hypoxia is associated with tissue injury and fibrosis but its functional role in fibroblast activation and tissue repair/regeneration is unknown. Using kidney injury as a model system, we demonstrate that injured epithelial cells produce an increased number of exosomes with defined genetic information to activate fibroblasts. Exosonnes released by injured epithelial cells promote proliferation, a-smooth muscle actin expression, F-actin expression, and type I collagen production in fibroblasts. Fibroblast activation is dependent on exosomes delivering TGF-beta 1 mRNA among other yet to be identified moieties. This study suggests that TGF-beta 1 mRNA transported by exosomes constitutes a rapid response to initiate tissue repair/regenerative responses and activation of fibroblasts when resident parenchyma is injured. The results also inform potential utility of exosome-targeted therapies to control tissue fibrosis. J Am Soc Nephrol 24: 385-392, 2013. doi: 10.1681/ASN.2012101031