Research progress on role of exosomes derived from different cells in hepatic stellate cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Kaimin ,  CHEN Gang , GAO Hongqiang , WANG Dongdong , HE Linghua , TONG Hongxing

Department of Hepatopancreatobiliary Surgery, Ganmei Hospital Affiliated to Kunming Medical University, Kunming 650032, P. R. China;

Corresponding?author：

CHEN Gang, Email: kmcg123@163.com

Keywords：

exosome; hepatic stellate cell; liver cirrhosis

DOI：

10.7507/1007-9424.202005015

Video：

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Objective To summarize the research progress on the role of exosomes derived from different sources in hepatic stellate cells.Method The experimental studies and clinical applications of exosomes from different cell sources effected on hepatic stellate cells were reviewed.Results In the occurrence and development of liver fibrosis pathological physiological process, the activation, proliferation, migration, apoptosis of hepatic stellate cells played the important roles on the development of liver fibrosis. In recent years, the study found that the exosomes derived from different sources contained active protein, mRNA, microRNA, long noncoding RNA, and lipid components involved in the biological function of hepatic stellate cells, realized the communication between cells, which played the important regulatory role in the formation of liver fibrosis.Conclusions Exosomes derived from different sources and their contents play an important regulatory role in occurrence and development of liver fibrosis. In the future, exosomes might become a new non-invasive diagnostic method for liver fibrosis to help its early diagnosis, and might also be used as a biological active carrier to achieve its targeted therapy for targeted tissues and cells.

Citation： LIU Kaimin, CHEN Gang, GAO Hongqiang, WANG Dongdong, HE Linghua, TONG Hongxing. Research progress on role of exosomes derived from different cells in hepatic stellate cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(1): 120-124. doi: 10.7507/1007-9424.202005015 Copy

1.	Carson JP, Ramm GA, Robinson MW, et al. Schistosome-induced fibrotic disease: the role of hepatic stellate cells. Trends Parasitol, 2018, 34(6): 524-540.
2.	Wake K. “Sternzellen” in the liver: perisinusoidal cells with special reference to storage of vitamin A. Am J Anat, 1971, 132(4): 429-462.
3.	Cai S, Cheng X, Pan X, et al. Emerging role of exosomes in liver physiology and pathology. Hepatol Res, 2017, 47(2): 194-203.
4.	Shen J, Huang CK, Yu H, et al. The role of exosomes in hepatitis, liver cirrhosis and hepatocellular carcinoma. J Cell Mol Med, 2017, 21(5): 986-992.
5.	Turturici G, Tinnirello R, Sconzo G, et al. Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages. Am J Physiol Cell Physiol, 2014, 306(7): C621-C633.
6.	Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell, 2016, 164(6): 1226-1232.
7.	Yá?ez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles, 2015, 4: 27066.
8.	Wang R, Ding Q, Yaqoob U, et al. Exosome adherence and internalization by hepatic stellate cells triggers sphingosine 1-phosphate-dependent migration. J Biol Chem, 2015, 290(52): 30684-30696.
9.	Qiu GG, Zheng GP, Ge MH, et al. Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs. Stem Cell Res Ther, 2018, 9(1): 320.
10.	Batagov AO, Kurochkin IV. Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3'-untranslated regions. Biol Direct, 2013, 8: 12.
11.	Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev, 2013, 22(6): 845-854.
12.	Jiang W, Tan Y, Cai M, et al. Human umbilical cord MSC-derived exosomes suppress the development of CCl4-induced liver injury through antioxidant effect. Stem Cells Int, 2018, 2018: 6079642.
13.	蔡夢潔. HucMSC來源的外泌體轉運 miR-373 和 Let-7b 緩解肝纖維化//嚴永敏主編. 臨床檢驗診斷學, 2018.
14.	Hyun J, Wang S, Kim J, et al. MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells. Sci Rep, 2015, 5: 14135.
15.	Lou G, Yang Y, Liu F, et al. MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis. J Cell Mol Med, 2017, 21(11): 2963-2973.
16.	李洪超, 王皙, 李莉, 等. 人脂肪干細胞來源外泌體對四氯化碳誘導肝纖維化模型大鼠的治療作用. 中國組織工程研究, 2020, 24(13): 1996-2004.
17.	Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol, 2017, 14(7): 397-411.
18.	Povero D, Panera N, Eguchi A, et al. Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-γ. Cell Mol Gastroenterol Hepatol, 2015, 1(6): 646-663.e4.
19.	Seo W, Eun HS, Kim SY, et al. Exosome-mediated activation of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by γδ T cells in liver fibrosis. Hepatology, 2016, 64(2): 616-631.
20.	Ma HY, Xu J, Liu X, et al. The role of IL-17 signaling in regulation of the liver-brain axis and intestinal permeability in alcoholic liver disease. Curr Pathobiol Rep, 2016, 4(1): 27-35.
21.	Devhare PB, Sasaki R, Shrivastava S, et al. Exosome-mediated intercellular communication between hepatitis C virus-infected hepatocytes and hepatic stellate cells. J Virol, 2017, 91(6): e02225-e02216.
22.	Dai X, Chen C, Xue J, et al. Exosomal MALAT1 derived from hepatic cells is involved in the activation of hepatic stellate cells via miRNA-26b in fibrosis induced by arsenite. Toxicol Lett, 2019, 316: 73-84.
23.	Zhang XW, Zhou JC, Peng D, et al. Disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation. Autophagy, 2020, 16(5): 782-796.
24.	Lee YS, Kim SY, Ko E, et al. Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells. Sci Rep, 2017, 7(1): 3710.
25.	Hirsova P, Ibrahim SH, Verma VK, et al. Extracellular vesicles in liver pathobiology: Small particles with big impact. Hepatology, 2016, 64(6): 2219-2233.
26.	Ban LA, Shackel NA, McLennan SV. Extracellular vesicles: a new frontier in biomarker discovery for non-alcoholic fatty liver disease. Int J Mol Sci, 2016, 17(3): 376.
27.	Bataller R, Brenner DA. Liver fibrosis. J Clin Invest, 2005, 115(2): 209-218.
28.	Scholten D, Osterreicher CH, Scholten A, et al. Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice. Gastroenterology, 2010, 139(3): 987-998.
29.	Dooley S, ten Dijke P. TGF-β in progression of liver disease. Cell Tissue Res, 2012, 347(1): 245-256.
30.	Chen L, Charrier A, Zhou Y, et al. Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery in exosomes from mouse or human hepatic stellate cells. Hepatology, 2014, 59(3): 1118-1129.
31.	Chen L, Chen R, Velazquez VM, et al. Fibrogenic signaling is suppressed in hepatic stellate cells through targeting of connective tissue growth factor (CCN2) by cellular or exosomal microRNA-199a-5p. Am J Pathol, 2016, 186(11): 2921-2933.
32.	Chen L, Brigstock DR. Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are novel receptors for HSC-derived exosomes. FEBS Lett, 2016, 590(23): 4263-4274.
33.	Chen L, Yao X, Yao H, et al. Exosomal miR-103-3p from LPS-activated THP-1 macrophage contributes to the activation of hepatic stellate cells. FASEB J, 2020, 34(4): 5178-5192.
34.	Liu R, Li X, Zhu W, et al. Cholangiocyte-derived exosomal long noncoding RNAH19 promotes hepatic stellate cell activation and cholestatic liver fibrosis. Hepatology, 2019, 70(4): 1317-1335.
35.	Li X, Liu R, Huang Z, et al. Cholangiocyte-derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans. Hepatology, 2018, 68(2): 599-615.
36.	Kim DK, Cho YE, Komarow HD, et al. Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells, and promote their activation. Proc Natl Acad Sci USA, 2018, 115(45): E10692-E10701.
37.	Borges FT, Melo SA, ?zdemir BC, et al. TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Nephrol, 201, 24(24): 385-392.

1. Carson JP, Ramm GA, Robinson MW, et al. Schistosome-induced fibrotic disease: the role of hepatic stellate cells. Trends Parasitol, 2018, 34(6): 524-540.
2. Wake K. “Sternzellen” in the liver: perisinusoidal cells with special reference to storage of vitamin A. Am J Anat, 1971, 132(4): 429-462.
3. Cai S, Cheng X, Pan X, et al. Emerging role of exosomes in liver physiology and pathology. Hepatol Res, 2017, 47(2): 194-203.
4. Shen J, Huang CK, Yu H, et al. The role of exosomes in hepatitis, liver cirrhosis and hepatocellular carcinoma. J Cell Mol Med, 2017, 21(5): 986-992.
5. Turturici G, Tinnirello R, Sconzo G, et al. Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages. Am J Physiol Cell Physiol, 2014, 306(7): C621-C633.
6. Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell, 2016, 164(6): 1226-1232.
7. Yá?ez-Mó M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles, 2015, 4: 27066.
8. Wang R, Ding Q, Yaqoob U, et al. Exosome adherence and internalization by hepatic stellate cells triggers sphingosine 1-phosphate-dependent migration. J Biol Chem, 2015, 290(52): 30684-30696.
9. Qiu GG, Zheng GP, Ge MH, et al. Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs. Stem Cell Res Ther, 2018, 9(1): 320.
10. Batagov AO, Kurochkin IV. Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3'-untranslated regions. Biol Direct, 2013, 8: 12.
11. Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev, 2013, 22(6): 845-854.
12. Jiang W, Tan Y, Cai M, et al. Human umbilical cord MSC-derived exosomes suppress the development of CCl4-induced liver injury through antioxidant effect. Stem Cells Int, 2018, 2018: 6079642.
13. 蔡夢潔. HucMSC來源的外泌體轉運 miR-373 和 Let-7b 緩解肝纖維化//嚴永敏主編. 臨床檢驗診斷學, 2018.
14. Hyun J, Wang S, Kim J, et al. MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells. Sci Rep, 2015, 5: 14135.
15. Lou G, Yang Y, Liu F, et al. MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis. J Cell Mol Med, 2017, 21(11): 2963-2973.
16. 李洪超, 王皙, 李莉, 等. 人脂肪干細胞來源外泌體對四氯化碳誘導肝纖維化模型大鼠的治療作用. 中國組織工程研究, 2020, 24(13): 1996-2004.
17. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol, 2017, 14(7): 397-411.
18. Povero D, Panera N, Eguchi A, et al. Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-γ. Cell Mol Gastroenterol Hepatol, 2015, 1(6): 646-663.e4.
19. Seo W, Eun HS, Kim SY, et al. Exosome-mediated activation of toll-like receptor 3 in stellate cells stimulates interleukin-17 production by γδ T cells in liver fibrosis. Hepatology, 2016, 64(2): 616-631.
20. Ma HY, Xu J, Liu X, et al. The role of IL-17 signaling in regulation of the liver-brain axis and intestinal permeability in alcoholic liver disease. Curr Pathobiol Rep, 2016, 4(1): 27-35.
21. Devhare PB, Sasaki R, Shrivastava S, et al. Exosome-mediated intercellular communication between hepatitis C virus-infected hepatocytes and hepatic stellate cells. J Virol, 2017, 91(6): e02225-e02216.
22. Dai X, Chen C, Xue J, et al. Exosomal MALAT1 derived from hepatic cells is involved in the activation of hepatic stellate cells via miRNA-26b in fibrosis induced by arsenite. Toxicol Lett, 2019, 316: 73-84.
23. Zhang XW, Zhou JC, Peng D, et al. Disrupting the TRIB3-SQSTM1 interaction reduces liver fibrosis by restoring autophagy and suppressing exosome-mediated HSC activation. Autophagy, 2020, 16(5): 782-796.
24. Lee YS, Kim SY, Ko E, et al. Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells. Sci Rep, 2017, 7(1): 3710.
25. Hirsova P, Ibrahim SH, Verma VK, et al. Extracellular vesicles in liver pathobiology: Small particles with big impact. Hepatology, 2016, 64(6): 2219-2233.
26. Ban LA, Shackel NA, McLennan SV. Extracellular vesicles: a new frontier in biomarker discovery for non-alcoholic fatty liver disease. Int J Mol Sci, 2016, 17(3): 376.
27. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest, 2005, 115(2): 209-218.
28. Scholten D, Osterreicher CH, Scholten A, et al. Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice. Gastroenterology, 2010, 139(3): 987-998.
29. Dooley S, ten Dijke P. TGF-β in progression of liver disease. Cell Tissue Res, 2012, 347(1): 245-256.
30. Chen L, Charrier A, Zhou Y, et al. Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery in exosomes from mouse or human hepatic stellate cells. Hepatology, 2014, 59(3): 1118-1129.
31. Chen L, Chen R, Velazquez VM, et al. Fibrogenic signaling is suppressed in hepatic stellate cells through targeting of connective tissue growth factor (CCN2) by cellular or exosomal microRNA-199a-5p. Am J Pathol, 2016, 186(11): 2921-2933.
32. Chen L, Brigstock DR. Integrins and heparan sulfate proteoglycans on hepatic stellate cells (HSC) are novel receptors for HSC-derived exosomes. FEBS Lett, 2016, 590(23): 4263-4274.
33. Chen L, Yao X, Yao H, et al. Exosomal miR-103-3p from LPS-activated THP-1 macrophage contributes to the activation of hepatic stellate cells. FASEB J, 2020, 34(4): 5178-5192.
34. Liu R, Li X, Zhu W, et al. Cholangiocyte-derived exosomal long noncoding RNAH19 promotes hepatic stellate cell activation and cholestatic liver fibrosis. Hepatology, 2019, 70(4): 1317-1335.
35. Li X, Liu R, Huang Z, et al. Cholangiocyte-derived exosomal long noncoding RNA H19 promotes cholestatic liver injury in mouse and humans. Hepatology, 2018, 68(2): 599-615.
36. Kim DK, Cho YE, Komarow HD, et al. Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells, and promote their activation. Proc Natl Acad Sci USA, 2018, 115(45): E10692-E10701.
37. Borges FT, Melo SA, ?zdemir BC, et al. TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Nephrol, 201, 24(24): 385-392.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress on role of exosomes derived from different cells in hepatic stellate cells

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