基于外泌体的细胞间的通讯方式日益被广泛关注。醛固酮是促肝纤维化的重要物质，其氧化效应可介导肝窦内皮细胞（LSEC）与肝星状细胞（HSC）的相互作用，促进肝窦毛细血管化及肝纤维化形成。然而，外泌体如何介导上述两种细胞间的通讯这一重要科学问题鲜见报道。我们的前期工作发现：醛固酮可引起LSEC mTOR表达升高，自噬减低，多囊泡体增多，LSEC及其外泌体中GAS5 lncRNA水平下降, miR-21表达上调，醛固酮诱导的LSEC外泌体可促进HSC活化，然而机制不明。由此，我们萌发探讨醛固酮如何通过外泌体途径调控LSEC与HSC之间的通讯之设想。本研究以外泌体为纽带将LSEC和HSC连结一体，从体内、外层面验证“醛固酮通过mTOR抑制LSEC自噬，促进外泌体分泌及诱发外泌体中miR-21/GAS5lncRNA失衡，介导肝星状细胞活化增殖”之假说。本研究为拓展醛固酮在肝纤维化的调控机制提供新思路。

Exosomes, which mediate intercellular communication, is gaining more and more attention in recent year. Aldosterone, an important promoter for liver fibrosis, mediates the interaction between liver sinusoidal endothelial cells (LSEC) and hepatic stellate cell (HCS) by inducing oxidative stress, leading to sinusoid capillarisation and liver fibrogenesis. However, how exosomes mediate the intercellular communication between LSEC and HCS has not been reported. Our preliminary studies showed that aldosterone treatment increased mTOR protein level and suppressed the level of autophagy in LSEC, while multivesicular bodys (MVBs) level was increased. Moreover, the level of GAS5 lncRNA was down-regulated while miR-21 level was up-regulated in both LSEC and exosomes. Finally, the aldosterone induced LSEC-derived exosomes could activate HSC, with the detail mechanisms remaining unclear. Consequently, we come up with the idea to explore how exosomes regulate the intercellular communication between LSEC and HSCs. In this study, we intergrate LSEC with HSC by exosomes, and prospect to perform in vivo and in vitro study to confirm the hypothesis: aldosterone induces LSEC autophagy by upregulating mTOR, which promotes exosomes secretion and disturbs the balance between miR-21 and GAS5 lncRNA in exosomes and ultimately regulates the activation and proliferation of HSCs. This project provides a novel pathway to study of liver fibrosis.