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羊膜来源的外泌体促进其抗纤维化作用。

Exosomes Secreted from Amniotic Membrane Contribute to Its Anti-Fibrotic Activity.

机构信息

Laboratory for Biomaterials Research, Department of Chemistry and Chemical Biology, Rutgers University, 145 Bevier Rd., Piscataway, NJ 08854, USA.

Smith & Nephew, 7015 Albert Einstein Drive, Columbia, MD 21046, USA.

出版信息

Int J Mol Sci. 2021 Feb 19;22(4):2055. doi: 10.3390/ijms22042055.

DOI:10.3390/ijms22042055
PMID:33669673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7922650/
Abstract

Amniotic membranes (AM) have anti-fibrotic activity. Exosomes (nano-sized vesicles) function as conduits for intercellular transfer and contain all the necessary components to induce the resolution of fibrosis. In this study, we tested the hypothesis that the anti-fibrotic activity of AM is mediated by exosomes. AM-derived exosomes or amniotic stromal cell-derived exosomes were isolated and characterized. Anti-fibrotic activity of exosomes was evaluated using human hepatic stellate cells (LX-2), an in vitro model of fibrosis. Exosomes isolated from AM tissue-conditioned media had an average size of 75 nm. Exosomes significantly inhibited the proliferation of TGFβ1-activated LX-2 but had no effect on the proliferation of non-activated LX-2 cells. Exosomes also reduced the migration of LX-2 in a scratch wound assay. Furthermore, exosomes reduced the gene expression of pro-fibrotic markers such as COL1A1, ACTA, and TGFβ1 in LX-2 cells. Interestingly, exosomes isolated from AM tissue under hypoxic conditions seemed to show a stronger anti-fibrotic activity than exosomes isolated from tissue under normoxic conditions. Exosomes released by in vitro cultured AM stromal cells were smaller in size compared with tissue exosomes and also showed anti-fibrotic activity on LX-2 cells. In conclusion, AM-tissue-released exosomes contribute to the anti-fibrotic activity of AM. This is the first report of isolation, characterization, and functional evaluation of exosomes derived from amniotic tissues with the direct comparison between tissue-derived exosomes and cultured cell-derived exosomes.

摘要

羊膜（AM）具有抗纤维化活性。外泌体（纳米大小的囊泡）作为细胞间转移的导管，包含诱导纤维化消退所需的所有成分。在这项研究中，我们检验了 AM 的抗纤维化活性是由外泌体介导的假设。分离并鉴定了 AM 来源的外泌体或羊膜基质细胞来源的外泌体。使用体外纤维化模型人肝星状细胞（LX-2）评估外泌体的抗纤维化活性。AM 组织条件培养基中分离的外泌体平均大小为 75nm。外泌体显著抑制 TGFβ1 激活的 LX-2 的增殖，但对非激活的 LX-2 细胞的增殖没有影响。外泌体还减少了划痕伤口试验中 LX-2 的迁移。此外，外泌体降低了 LX-2 细胞中促纤维化标志物如 COL1A1、ACTA 和 TGFβ1 的基因表达。有趣的是，与正常氧条件下组织分离的外泌体相比，缺氧条件下 AM 组织分离的外泌体似乎表现出更强的抗纤维化活性。与组织外泌体相比，体外培养的 AM 基质细胞释放的外泌体体积较小，对 LX-2 细胞也具有抗纤维化活性。总之，AM 组织释放的外泌体有助于 AM 的抗纤维化活性。这是首次报道从羊膜组织中分离、鉴定和功能评价外泌体，并直接比较组织来源的外泌体和培养细胞来源的外泌体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a15/7922650/dc05ae1a4df8/ijms-22-02055-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a15/7922650/0c0dba6f38ca/ijms-22-02055-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a15/7922650/dc05ae1a4df8/ijms-22-02055-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a15/7922650/0c0dba6f38ca/ijms-22-02055-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a15/7922650/0a5ba276da61/ijms-22-02055-g004.jpg
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