Small extracellular vesicles with LncRNA H19 "overload": YAP Regulation as a Tendon Repair Therapeutic Tactic.
Small extracellular vesicles with LncRNA H19 "overload": YAP Regulation as a Tendon Repair Therapeutic Tactic.
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LncRNA H19“超载”的小细胞外囊泡：YAP 调节作为肌腱修复治疗策略
DOI：
10.1016/j.isci.2021.102200
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发表时间：
2021-03-19
期刊：
影响因子：
5.8
通讯作者：
Guo SC
中科院分区：
文献类型：
--
作者：
Tao SC;Huang JY;Li ZX;Zhan S;Guo SC
肌腱损伤的功能性愈合仍然是一个巨大的挑战。小细胞外囊泡（sEV）作为促再生剂已经受到关注。H19基因的过表达可以促进肌腱再生，但其机制尚未完全阐明，需要可靠的长链非编码RNA（longnoncodingRNA，LncRNA）递送方法。我们确定了H19的下游机制，即通过H19-PP 1-雅普轴激活yes相关蛋白（雅普）。我们用基于CRISPR-dCas 9的hnRNP A2/B1活化（H19-CP-TSPC）建立了稳定过表达H19的肌腱干/祖细胞（TSPC）。H19-OL-sEV（H19“过载”sEV）可以有效地从H19-CP-TSPC产生。只有H19-OL-sEV能够显著负载大量的H19，而不是其他竞争对手，H19-OL-sEV促进肌腱愈合的潜力远远优于其他竞争对手。我们的研究建立了一种相对可靠的方法，将LncRNA富集到sEV中，为基于模块化sEV的治疗提供了新的提示，模块化sEV代表了肌腱再生的潜在策略。H19过表达增强肌腱再生H19去磷酸化并激活雅普hnRNP A2/B1协助H19富集成sEV H19-OL-sEV促进肌腱再生分子生物学;细胞生物学;干细胞研究
Functional healing of tendon injuries remains a great challenge. Small extracellular vesicles (sEVs) have received attention as pro-regenerative agents. H19 overexpression could bring tendon regenerative ability, but the mechanism is still not fully elucidated, and reliable method for delivery of long non-coding RNAs (LncRNAs) was demanded. We identified the downstream mechanism of H19, the activation of yes-associated protein (YAP) via the H19-PP1-YAP axis. We established tendon stem/progenitor cells (TSPCs) stably overexpressing H19 with CRISPR-dCas9-based hnRNP A2/B1 activation (H19-CP-TSPCs). H19-OL-sEVs (H19 “overloading” sEVs) could be produced effectively from H19-CP-TSPCs. Only H19-OL-sEVs were able to significantly load large amounts of H19 rather than other competitors, and the potential of H19-OL-sEVs to promote tendon healing was far better than that of other competitors. Our study established a relatively reliable method for enrichment of LncRNAs into sEVs, providing new hints for modularized sEV-based therapies, and modularized sEVs represented a potential strategy for tendon regeneration. H19 overexpression enhances tendon regeneration H19 dephosphorylates and activates YAP hnRNP A2/B1 assists the enrichment of H19 into sEVs H19-OL-sEVs promote tendon regeneration Molecular Biology; Cell Biology; Stem Cells Research
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影响因子：
8
作者：
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通讯作者：
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影响因子：
82.9
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Goodarzi, Hani;Najafabadi, Hamed S.;Oikonomou, Panos;Greco, Todd M.;Fish, Lisa;Salavati, Reza;Cristea, Ileana M.;Tavazoie, Saeed
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Tavazoie, Saeed
影响因子：
10.5
作者：
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通讯作者：
Dutta A
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影响因子：
9.7
作者：
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通讯作者：
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