PDF(Pubmed)
Abstract：
UNASSIGNED: The liver\'s regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver\'s interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear.
UNASSIGNED: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed β-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of β-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a β-sitosterol diet on liver regeneration was verified in mice.
UNASSIGNED: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70-130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified β-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased β-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls.
UNASSIGNED: Liver-derived EVPs promote regeneration after partial hepatectomy. β-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.
UNASSIGNED: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed β-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of β-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a β-sitosterol diet on liver regeneration was verified in mice.
UNASSIGNED: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70-130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified β-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased β-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls.
UNASSIGNED: Liver-derived EVPs promote regeneration after partial hepatectomy. β-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.
摘要：
■肝脏的再生能力使其能够在受伤后自我修复。细胞外囊泡和颗粒（EVPs）在肝脏的间质空间是至关重要的信号转导，新陈代谢，和免疫调节。了解肝源性EVPs在再生中的作用和机制是重要的，尤其是部分肝切除术后，机制尚不清楚。
■在小鼠中建立了70％肝切除模型，和EVP分离并使用电子显微镜进行表征，纳米表征，和蛋白质印迹分析。结合代谢组和转录组分析显示，在再生过程中EVP中β-谷甾醇富集和Hedgehog信号通路的激活。利用qRT-PCR方法鉴定了β-谷甾醇在EVPs中对Hedgehog通路及其靶标的作用,蛋白质印迹分析。使用双荧光素酶测定法测定通过该途径对肉毒碱合成的调节。在小鼠中验证了β-谷甾醇饮食对肝再生的影响。
■70%肝切除术后，肝脏成功再生，无肝功能衰竭或死亡。手术后24小时,组织染色显示短暂性再生相关脂肪变性（TRAS），在48小时时Ki67阳性增加。EVP表现出球形脂质双层结构，粒径为70-130nm。证实了肝脏来源的EVP中的CD9、CD63和CD81。转录组学和代谢组学分析显示，补充EVP可显着促进肉碱合成和脂肪酸氧化。组织染色证实了用EVP补充加速的TRAS分辨率和增强的肝再生。质谱鉴定了EVPs中的β-谷甾醇，与Smo蛋白结合，激活Hedgehog通路.这导致Gli3的核转运，刺激Sett5转录并诱导肉碱合成，从而加速脂肪酸氧化。与对照组相比，β-谷甾醇摄入量增加的小鼠显示出更快的TRAS分辨率和肝脏再生。
■肝源性EVPs促进肝部分切除术后再生。来自EVPs的β-谷甾醇通过激活Hedgehog信号通路加速脂肪酸氧化并促进肝脏再生。
■在小鼠中建立了70％肝切除模型，和EVP分离并使用电子显微镜进行表征，纳米表征，和蛋白质印迹分析。结合代谢组和转录组分析显示，在再生过程中EVP中β-谷甾醇富集和Hedgehog信号通路的激活。利用qRT-PCR方法鉴定了β-谷甾醇在EVPs中对Hedgehog通路及其靶标的作用,蛋白质印迹分析。使用双荧光素酶测定法测定通过该途径对肉毒碱合成的调节。在小鼠中验证了β-谷甾醇饮食对肝再生的影响。
■70%肝切除术后，肝脏成功再生，无肝功能衰竭或死亡。手术后24小时,组织染色显示短暂性再生相关脂肪变性（TRAS），在48小时时Ki67阳性增加。EVP表现出球形脂质双层结构，粒径为70-130nm。证实了肝脏来源的EVP中的CD9、CD63和CD81。转录组学和代谢组学分析显示，补充EVP可显着促进肉碱合成和脂肪酸氧化。组织染色证实了用EVP补充加速的TRAS分辨率和增强的肝再生。质谱鉴定了EVPs中的β-谷甾醇，与Smo蛋白结合，激活Hedgehog通路.这导致Gli3的核转运，刺激Sett5转录并诱导肉碱合成，从而加速脂肪酸氧化。与对照组相比，β-谷甾醇摄入量增加的小鼠显示出更快的TRAS分辨率和肝脏再生。
■肝源性EVPs促进肝部分切除术后再生。来自EVPs的β-谷甾醇通过激活Hedgehog信号通路加速脂肪酸氧化并促进肝脏再生。
