{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:09:00Z","timestamp":1740146940436,"version":"3.37.3"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070637"],"award-info":[{"award-number":["82070637"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>This study evaluated the effect of microvesicles(MVs) from quiescent and TGF-\u03b21 stimulated hepatic stellate cells (HSC-MVs, TGF-\u03b21HSC-MVs) on H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced human umbilical vein endothelial cells (HUVECs) injury and CCl<jats:sub>4<\/jats:sub>-induced rat hepatic vascular injury.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>HUVECs were exposed to hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) to establish a model for vascular endothelial cell injury. HSC-MVs or TGF-\u03b21HSC-MVs were co-cultured with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-treated HUVECs, respectively. Indicators including cell survival rate, apoptosis rate, oxidative stress, migration, invasion, and angiogenesis were measured. Simultaneously, the expression of proteins such as PI3K, AKT, MEK1+MEK2, ERK1+ERK2, VEGF, eNOS, and CXCR4 was assessed, along with activated caspase-3. SD rats were intraperitoneally injected with CCl<jats:sub>4<\/jats:sub> twice a week for 10 weeks to induce liver injury models. HSC-MVs or TGF-\u03b21HSC-MVs were injected into the tail vein of rats. Liver and hepatic vascular damage were also detected.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>In H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-treated HUVECs, HSC-MVs increased cell viability, reduced cytotoxicity and apoptosis, improved oxidative stress, migration, and angiogenesis, and upregulated protein expression of PI3K, AKT, MEK1\/2, ERK1\/2, VEGF, eNOS, and CXCR4. Conversely, <jats:sup>TGF-\u03b21<\/jats:sup>HSC-MVs exhibited opposite effects. CCl<jats:sub>4<\/jats:sub>- induced rat hepatic injury model, HSC-MVs reduced the release of ALT and AST, hepatic inflammation, fatty deformation, and liver fibrosis. HSC-MVs also downregulated the protein expression of CD31 and CD34. Conversely, TGF-\u03b21HSC-MVs demonstrated opposite effects.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>HSC-MVs demonstrated a protective effect on H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-treated HUVECs and CCl<jats:sub>4<\/jats:sub>-induced rat hepatic injury, while TGF-\u03b21HSC-MVs had an aggravating effect. The effects of MVs involve PI3K\/AKT\/VEGF, CXCR4, and MEK\/ERK\/eNOS pathways.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0306775","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T17:44:49Z","timestamp":1720633489000},"page":"e0306775","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microvesicles from quiescent and TGF-\u03b21 stimulated hepatic stellate cells: Divergent impact on hepatic vascular injury"],"prefix":"10.1371","volume":"19","author":[{"given":"Jianlong","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhirong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anzhi","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qunwen","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7911-2460","authenticated-orcid":true,"given":"Huilai","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"issue":"4","key":"pone.0306775.ref001","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1002\/hep.30056","article-title":"Acute-on-Chronic 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