Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2

Hepatic stellate cells (HSCs), previously described for liver-specific mesenchymal stem cells (MSCs), appear to contribute to liver regeneration. Microvesicles (MVs) are nanoscale membrane fragments, which can regulate target cell function by transferring contents from their parent cells. The aim of...

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Main Authors: Renwei Huang, Qunwen Pan, Xiaotang Ma, Yan Wang, Yaolong Liang, Bingyan Dai, Xiaorong Liao, Mingyi Li, Huilai Miao
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/8357567
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author Renwei Huang
Qunwen Pan
Xiaotang Ma
Yan Wang
Yaolong Liang
Bingyan Dai
Xiaorong Liao
Mingyi Li
Huilai Miao
author_facet Renwei Huang
Qunwen Pan
Xiaotang Ma
Yan Wang
Yaolong Liang
Bingyan Dai
Xiaorong Liao
Mingyi Li
Huilai Miao
author_sort Renwei Huang
collection DOAJ
description Hepatic stellate cells (HSCs), previously described for liver-specific mesenchymal stem cells (MSCs), appear to contribute to liver regeneration. Microvesicles (MVs) are nanoscale membrane fragments, which can regulate target cell function by transferring contents from their parent cells. The aim of this study was to investigate the effect of HSC-derived MVs on xenobiotic-induced liver injury. Rat and human hepatocytes, BRL-3A and HL-7702, were used to build hepatocytes injury models by n-acetyl-p-aminophenol n-(APAP) or H2O2 treatment. MVs were prepared from human and rat HSCs, LX-2, and HST-T6 and, respectively, added to injured BRL-3A and HL-7702 hepatocytes. MTT assay was utilized to determine cell proliferation. Cell apoptosis was analyzed by flow cytometry and hoechst33258 staining. Western blot was used for analyzing the expression of activated caspase-3. Liver injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in culture medium were also assessed. Results showed that (1) HSC-MVs derived from LX-2 and HST-T6 were positive to CD90 and annexin V surface markers; (2) HSC-MVs dose-dependently improved the viability of hepatocytes in both injury models; (3) HSC-MVs dose-dependently inhibited the APAP/H2O2 induced hepatocytes apoptosis and activated caspase-3 expression and leakage of LDH, ALT, and AST. Our results demonstrate that HSC-derived MVs protect hepatocytes from toxicant-induced injury.
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spelling doaj-art-0708b098148842a2876f802a66c2fe092025-02-03T00:59:26ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/83575678357567Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2Renwei Huang0Qunwen Pan1Xiaotang Ma2Yan Wang3Yaolong Liang4Bingyan Dai5Xiaorong Liao6Mingyi Li7Huilai Miao8Department of Hepatobiliary Surgery, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaDepartment of Hepatobiliary Surgery, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaDepartment of Hepatobiliary Surgery, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaDepartment of Hepatobiliary Surgery, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, ChinaHepatic stellate cells (HSCs), previously described for liver-specific mesenchymal stem cells (MSCs), appear to contribute to liver regeneration. Microvesicles (MVs) are nanoscale membrane fragments, which can regulate target cell function by transferring contents from their parent cells. The aim of this study was to investigate the effect of HSC-derived MVs on xenobiotic-induced liver injury. Rat and human hepatocytes, BRL-3A and HL-7702, were used to build hepatocytes injury models by n-acetyl-p-aminophenol n-(APAP) or H2O2 treatment. MVs were prepared from human and rat HSCs, LX-2, and HST-T6 and, respectively, added to injured BRL-3A and HL-7702 hepatocytes. MTT assay was utilized to determine cell proliferation. Cell apoptosis was analyzed by flow cytometry and hoechst33258 staining. Western blot was used for analyzing the expression of activated caspase-3. Liver injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in culture medium were also assessed. Results showed that (1) HSC-MVs derived from LX-2 and HST-T6 were positive to CD90 and annexin V surface markers; (2) HSC-MVs dose-dependently improved the viability of hepatocytes in both injury models; (3) HSC-MVs dose-dependently inhibited the APAP/H2O2 induced hepatocytes apoptosis and activated caspase-3 expression and leakage of LDH, ALT, and AST. Our results demonstrate that HSC-derived MVs protect hepatocytes from toxicant-induced injury.http://dx.doi.org/10.1155/2016/8357567
spellingShingle Renwei Huang
Qunwen Pan
Xiaotang Ma
Yan Wang
Yaolong Liang
Bingyan Dai
Xiaorong Liao
Mingyi Li
Huilai Miao
Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2
Stem Cells International
title Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2
title_full Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2
title_fullStr Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2
title_full_unstemmed Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2
title_short Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2
title_sort hepatic stellate cell derived microvesicles prevent hepatocytes from injury induced by apap h2o2
url http://dx.doi.org/10.1155/2016/8357567
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