Inhibition of liver lipid deposition by exosomes derived from hepatocytes in mice with nonalcoholic fatty liver
WU Yanshuang1, WANG Yanjin1, YANG Fuji1, YAN Yongmin1,2
(1. School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013; 2. Department of Liver Disease, Third Hospital of Zhenjiang, Zhenjiang Jiangsu 212005, China)
Abstract:[Abstract]Objective: To investigate the effect of exosomes derived from hepatocytes(LO2-Ex) on liver lipid deposition in mice with nonalcoholic fatty liver induced by highfat diet. Methods: Normal human hepatocyte line LO2 cells were cultured and LO2-Ex was extracted by ultracentrifugation. The particle size and concentration of exosomes were measured by nanosight nanoparticle analysis system, the morphology of exosomes was observed by transmission electron microscope, and the markers of exosomes were detected by Western blotting. C57BL/6 male mice were fed with highfat diet for 10 weeks to establish the mice model of nonalcoholic fatty liver. From the 11th week, LO2-Ex was injected into the caudal vein continuously for 4 weeks, and the liver tissue was collected after 4 weeks, the liver tissue structure was observed by HE staining, the liver index(liver mass / net weight) was calculated, the lipid deposition in the liver was detected by oil red O staining, and the collagen deposition in the liver was observed by Sirius red staining. Results: LO2-Ex, a particle size of about 120 nm, has a lipid bilayer structure characteristic of exosomes. It expresses exosome specific proteins CD9 and TSG101, but does not express Calnexin. Compared with the model group, the liver surface of mice in LO2-Ex group were ruddy, delicate and shiny. LO2Ex can reduce the weight of mice and improve the liver index of mice. HE staining, oil red O staining and Sirius red staining showed that LO2-Ex reduced vacuolar degeneration, fat deposition and collagen deposition in liver tissues. Conclusion:LO2-Ex can inhibit lipid deposition in liver tissues and inhibit the progression of nonalcoholic fatty liver in mice.
武艳霜,王岩金,杨馥吉,等. 肝细胞外泌体抑制小鼠非酒精性脂肪肝脂质沉积[J]. 江苏大学学报:医学版, 2022, 22(04): 332-337.
WU Yanshuang1, WANG Yanjin1, YANG Fuji1, YAN Yongmin1,2. Inhibition of liver lipid deposition by exosomes derived from hepatocytes in mice with nonalcoholic fatty liver. Journal of Jiangsu University(Medicine Edition), 2022, 22(04): 332-337.
[1]Lazarus JV, Mark HE, Anstee QM, et al. Advancing the global public health agenda for NAFLD: a consensus statement[J]. Nat Rev Gastroenterol Hepatol, 2022, 19(1): 60-78.
[2]Tamaki N, Ajmera V, Loomba R. Noninvasive methods for imaging hepatic steatosis and their clinical importance in NAFLD[J]. Nat Rev Endocrinol, 2022, 18(1): 55-66.
[3]李昊翔,徐梦娇,袁婧,等. 2型糖尿病合并非酒精性脂肪肝患者血清白脂素浓度变化及其影响因素[J]. 江苏大学学报(医学版), 2019, 29(1): 62-66.
[4]尹贻倩,陈艺文,赵雨雪,等. 外泌体在结肠癌和成纤维细胞间交互影响中的作用研究进展[J]. 江苏大学学报(医学版),2022,32(2):180-184.
[5]Li C, Teixeira AF, Zhu HJ, et al. Cancer associatedfibroblastderived exosomes in cancer progression[J]. Mol Cancer, 2021, 20(1): 154.
[6]Wu D, Zhu H, Wang H. Extracellular vesicles in nonalcoholic fatty liver disease and alcoholic liver disease[J]. Front Physiol, 2021, 12: 707429.
[7]唐雨婷,乔佳琦,许文荣,等. 外泌体在糖尿病及其并发症中的作用研究进展[J]. 江苏大学学报(医学版), 2020, 30(4): 298-301.
[8]Cheng L, Yu P, Li F, et al. Human umbilical cordderived mesenchymal stem cellexosomal miR6275p ameliorates nonalcoholic fatty liver disease by repressing FTO expression[J]. Hum Cell, 2021, 34(6): 1697-1708.
[9]ElDerany MO, Abdel Hamid SG. Upregulation of miR965p by bone marrow mesenchymal stem cells and their exosomes alleviate nonalcoholic steatohepatitis: Emphasis on caspase2 signaling inhibition[J]. Biochem Pharmacol, 2021, 190: 114624.
[10]Scorletti E, Carr RM. A new perspective on NAFLD: Focusing on lipid droplets[J]. J Hepatol, 2022, 76(4): 934-945.
[11]Kumar S, Duan Q, Wu R, et al. Pathophysiological communication between hepatocytes and nonparenchymal cells in liver injury from NAFLD to liver fibrosis[J]. Adv Drug Deliv Rev, 2021, 176: 113869.
[12]Dorairaj V, Sulaiman SA, Abu N, et al. Extracellular vesicles in the development of the nonalcoholic fatty liver disease: an update[J]. Biomolecules, 2020, 10(11): 1494.
[13]Masoodi M, Gastaldelli A, HytylinenT, et al. Metabolomics and lipidomics in NAFLD: biomarkers and noninvasive diagnostic tests[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(12): 835-856.
[14]Ramai D, Facciorusso A, Vigandt E, et al. Progressive liver fibrosis in nonalcoholic fatty liver disease[J]. Cells, 2021, 10(12): 3401.
[15]江佳佳,吴佩佩,许文荣. 肿瘤外泌体标志物应用及靶向治疗进展[J]. 江苏大学学报(医学版), 2021, 31(1): 11-16.
[16]施晋升,王茂松,李本忠,等. 食管癌细胞来源的外泌体促进人脐静脉血管内皮细胞血管生成[J]. 江苏大学学报(医学版), 2021, 31(5): 412-416, 420.
[17]Seo W, Eun HS, Kim SY, et al. Exosomemediated activation of tolllike receptor 3 in stellate cells stimulates interleukin17 production by γδ T cells in liver fibrosis[J]. Hepatology, 2016, 64(2): 616-631.
[18]Wu J, Dong T, Chen T, et al. Hepatic exosomederived miR130a3p attenuates glucose intolerance via suppressing PHLPP2 gene in adipocyte[J]. Metabolism, 2020, 103: 154006.
[19]Liu XL, Pan Q, Cao HX, et al. Lipotoxic hepatocytederived exosomal microRNA 1925p activates macrophages through Rictor/Akt/Forkhead Box transcription factor O1 signaling in nonalcoholic fatty liver disease[J]. Hepatology, 2020, 72(2): 454-469.
[20]Yan Y, Jiang W, Tan Y, et al. hucMSC exosomederived GPX1 is required for the recovery of hepatic oxidant injury[J]. Mol Ther, 2017, 25(2): 465-479.
[21]Psaraki A, NtariL, Karakostas C, et al. Extracellular vesicles derived from mesenchymal stem/stromal cells: the regenerative impact in liver diseases[J]. Hepatology, 2021, 75(6): 1590-1603.
[22]Nojima H, Freeman CM, Schuster RM, et al. Hepatocyte exosomes mediate liver repair and regeneration via sphingosine1phosphate[J]. J Hepatol, 2016, 64(1): 60-68.
[23]Zhao WJ, Bian YP, Wang QH, et al. Blueberryderived exosomeslike nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress[J]. Acta Pharmacol Sin, 2022, 43(3): 645-658.
[24]Hou X, Yin S, Ren R, et al. Myeloidcellspecific IL6 signaling promotes microRNA223enriched exosome production to attenuate NAFLDassociated fibrosis[J]. Hepatology, 2021, 74(1): 116-132.