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Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis
BACKGROUNDS/AIMS: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the d...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367781/ https://www.ncbi.nlm.nih.gov/pubmed/28346483 http://dx.doi.org/10.1371/journal.pone.0174218 |
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author | Jin, Xi Liu, Jiang Chen, Yi-peng Xiang, Zun Ding, Jie-xia Li, You-ming |
author_facet | Jin, Xi Liu, Jiang Chen, Yi-peng Xiang, Zun Ding, Jie-xia Li, You-ming |
author_sort | Jin, Xi |
collection | PubMed |
description | BACKGROUNDS/AIMS: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. METHODS: NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H(2)O(2) and ATP levels were measured for mechanism exploration. RESULTS: Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H(2)O(2) and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels. CONCLUSIONS: The miR-146-HDMCP-ATP/H(2)O(2) pathway may provide novel mechanism and treatment option for NASH. |
format | Online Article Text |
id | pubmed-5367781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53677812017-04-06 Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis Jin, Xi Liu, Jiang Chen, Yi-peng Xiang, Zun Ding, Jie-xia Li, You-ming PLoS One Research Article BACKGROUNDS/AIMS: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. METHODS: NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H(2)O(2) and ATP levels were measured for mechanism exploration. RESULTS: Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H(2)O(2) and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels. CONCLUSIONS: The miR-146-HDMCP-ATP/H(2)O(2) pathway may provide novel mechanism and treatment option for NASH. Public Library of Science 2017-03-27 /pmc/articles/PMC5367781/ /pubmed/28346483 http://dx.doi.org/10.1371/journal.pone.0174218 Text en © 2017 Jin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jin, Xi Liu, Jiang Chen, Yi-peng Xiang, Zun Ding, Jie-xia Li, You-ming Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis |
title | Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis |
title_full | Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis |
title_fullStr | Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis |
title_full_unstemmed | Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis |
title_short | Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis |
title_sort | effect of mir-146 targeted hdmcp up-regulation in the pathogenesis of nonalcoholic steatohepatitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367781/ https://www.ncbi.nlm.nih.gov/pubmed/28346483 http://dx.doi.org/10.1371/journal.pone.0174218 |
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