{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:03:28Z","timestamp":1790885008319,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470855"],"award-info":[{"award-number":["81470855"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003397","name":"Huazhong University of Science and Technology","doi-asserted-by":"publisher","award":["2017KFYXJJ053"],"award-info":[{"award-number":["2017KFYXJJ053"]}],"id":[{"id":"10.13039\/501100003397","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013291","name":"Tongji Medical College, Huazhong University of Science and Technology","doi-asserted-by":"publisher","award":["500153003"],"award-info":[{"award-number":["500153003"]}],"id":[{"id":"10.13039\/501100013291","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The mechanism of exosomes derived from activated hepatic stellate cells (HSCs) involved in liver fibrosis is poorly understood. We previously reported that hypoxia\u2010inducible factor 1 (Hif\u20101) regulated HSC activation, and, therefore, we investigated in current work whether Hif\u20101 regulates exosome secretion and the metabolic switch of HSCs, thus affecting the metabolism of liver nonparenchymal cells. In this study, the characteristics of exosomes from HSCs were assessed\n                    <jats:italic>via<\/jats:italic>\n                    electron microscopy, Western blot analysis, and acetylcholinesterase activity. Confocal microscopy was used to measure the uptake of exosomes by quiescent HSCs, Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs). Hif\u20101\u03b1 was inhibited\n                    <jats:italic>via<\/jats:italic>\n                    2\u2010ME or specific small interfering RNAs to investigate its role in exosomes derived from HSCs. It was determined that glucose transporter 1 and pyruvate kinase M2 were increasingly expressed in fibrotic liver samples, cell lysates, and exosomes derived from activated HSCs. Exosomes released from HSCs were associated with activation and glucose uptake of HSCs. Delivery of exosomes from activated HSCs induced glycolysis of quiescent HSCs, KCs, and LSECs. Disruption of Hif\u20101 expression suppressed the glycolysis effect delivered by exosomes. Conclusively, our results demonstrated that exosomes secreted by activated HSCs affect the metabolic switch of liver nonparenchymal cells\n                    <jats:italic>via<\/jats:italic>\n                    delivery of glycolysis\u2010related proteins. These findings represent a novel mechanism that contributes to liver fibrosis and has significant implications for new diagnosis and treatment of liver diseases.\u2014Wan, L., Xia, T., Du, Y., Liu, J., Xie, Y., Zhang, Y., Guan, F., Wu, J., Wang, X., Shi, C. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells. FASEB J. 33, 8530\u20138542 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201802675r","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T19:45:51Z","timestamp":1554925551000},"page":"8530-8542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":123,"title":["Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells"],"prefix":"10.1096","volume":"33","author":[{"given":"Lu","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology Huazhong University of Science and Technology  Wuhan China"},{"name":"Department of Pathophysiology School of Basic Medicine Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Surgery Wuhan Third Hospital  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology School of Basic Medicine Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunwei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0479"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.043"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1285"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000493218"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17020173"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81132"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.09.002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/373295"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2015.07.010"},{"key":"e_1_2_8_11_1","first-page":"7","article-title":"How to face chronic liver disease: the sinusoidal perspective","volume":"4","author":"Fernandez-Iglesias A.","year":"2017","journal-title":"Front. 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