https://scholars.lib.ntu.edu.tw/handle/123456789/457846
標題: | Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression | 作者: | Huang Y.-J. PO-DA CHEN CHIH-YUAN LEE Yang S.-Y. MING-TSAN LIN Lee, Hsuan-Shu YAO-MING WU |
公開日期: | 2016 | 出版社: | BioMed Central Ltd. | 卷: | 23 | 期: | 1 | 來源出版物: | Journal of Biomedical Science | 摘要: | Background: Acetaminophen (APAP) overdose causes acute liver failure (ALF) in animals and humans via the rapid depletion of intracellular glutathione (GSH) and the generation of excess reactive oxygen species (ROS) that damage hepatocytes. Stem cell therapy is a potential treatment strategy for ALF. Methods: We isolated mesenchymal stem cells (MSCs) from mice omentum adipose tissue-derived stem cells (ASCs) and transplanted them into a mouse model of APAP-induced ALF to explore their therapeutic potential. In addition, we performed in vitro co-culture studies with omentum-derived ASCs and primary isolated hepatocytes to demonstrate the hepatoprotective effect of omentum-derived ASCs on hepatocytes that were subjected to APAP-induced damage. Result: ASC transplantation significantly improved the survival rate of mice with ALF and attenuated the severity of APAP-induced liver damage by suppressing cytochrome P450 activity to reduce the accumulation of toxic nitrotyrosine and the upregulation of NF-E2-related factor 2 (Nrf2) expression, resulting in an increase in the subsequent antioxidant activity. These effects protected the hepatocytes from APAP-induced damage through the suppression of downstream MAPK signal activation and inflammatory cytokine production. Conclusions: our results demonstrate that omentum-derived ASCs are an alternative source of ASCs that regulate the antioxidant response and may represent a beneficial therapeutic strategy for ALF. ? 2016 Huang et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84957433653&doi=10.1186%2fs12929-016-0231-x&partnerID=40&md5=f7fc6e14a5fca82e369a499115a65ee9 https://scholars.lib.ntu.edu.tw/handle/123456789/457846 |
ISSN: | 1021-7770 | DOI: | 10.1186/s12929-016-0231-x | SDG/關鍵字: | 3 nitrotyrosine; cytochrome P450; mitogen activated protein kinase; transcription factor Nrf2; cytochrome P450; Nfe2l2 protein, mouse; paracetamol; transcription factor Nrf2; acute liver failure; adipose tissue; animal cell; animal experiment; animal model; animal tissue; antioxidant activity; Article; cell isolation; coculture; controlled study; cytokine production; disease severity; in vitro study; liver cell; liver protection; male; mesenchymal stem cell transplantation; mouse; nonhuman; omentum; omentum adipose tissue derived stem cell; priority journal; protein expression; signal transduction; stem cell; survival rate; therapy effect; upregulation; animal; biosynthesis; chemically induced; drug effects; gene expression regulation; Liver Failure, Acute; metabolism; omentum; stem cell transplantation; Acetaminophen; Adipose Tissue; Animals; Cytochrome P-450 Enzyme System; Gene Expression Regulation, Enzymologic; Liver Failure, Acute; Male; Mice; NF-E2-Related Factor 2; Omentum; Stem Cell Transplantation; Stem Cells |
顯示於: | 醫學系 |
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