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Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration
BACKGROUND: Myocardial fibrosis is an important pathological change in many heart diseases, but its pathogenesis is very complex and has not yet been fully elucidated. The study was designed to examine whether endogenous sulfur dioxide (SO(2)) is a novel myocardial fibroblast proliferation and migra...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048932/ https://www.ncbi.nlm.nih.gov/pubmed/29998892 http://dx.doi.org/10.4103/0366-6999.235875 |
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author | Zhang, Lu-Lu Du, Jun-Bao Tang, Chao-Shu Jin, Hong-Fang Huang, Ya-Qian |
author_facet | Zhang, Lu-Lu Du, Jun-Bao Tang, Chao-Shu Jin, Hong-Fang Huang, Ya-Qian |
author_sort | Zhang, Lu-Lu |
collection | PubMed |
description | BACKGROUND: Myocardial fibrosis is an important pathological change in many heart diseases, but its pathogenesis is very complex and has not yet been fully elucidated. The study was designed to examine whether endogenous sulfur dioxide (SO(2)) is a novel myocardial fibroblast proliferation and migration inhibitor. METHODS: Primary rat myocardial fibroblasts were isolated and transfected with aspartate aminotransferase (AAT1 and AAT2) knockdown lentivirus or empty lentivirus. SO(2) content in the supernatant was determined with high-performance liquid chromatography, and the expressions of AAT1, AAT2, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated protein kinase (p-ERK), and total ERK (T-ERK) in the cells were detected. Cell migration was detected by wound healing test. Independent sample t-test (for two groups) and one-way analysis of variance (three or more groups) were used to analyze the results. RESULTS: Both AAT1 and AAT2 knockdown significantly reduced SO(2) levels (F = 31.46, P < 0.01) and AAT1/2 protein expression (AAT1, t = 12.67, P < 0.01; AAT2, t = 9.61, P < 0.01), but increased PCNA expression and Cell Counting Kit-8 (CCK-8) activity as well as the migration in rat primary myocardial fibroblasts (P < 0.01). Supplementation of SO(2) rather than pyruvate significantly inhibited the increase in proliferation and migration caused by AAT knockdown (P < 0.01). Mechanistically, the ratio of p-ERK to T-ERK was significantly increased in the AAT1/2 knockdown groups compared with that in the empty lentivirus group (AAT1, t = −7.36, P < 0.01; AAT2, t = −10.97, P < 0.01). Whereas PD98059, an inhibitor of ERK activation, successfully blocked AAT knockdown-induced PCNA upregulation (F = 74.01, P > 0.05), CCK-8 activation (F = 50.14, P > 0.05), and migration augmentation in myocardial fibroblasts (24 h, F = 37.08, P > 0.05; 48 h, F = 58.60, P > 0.05). CONCLUSION: Endogenous SO(2) might be a novel myocardial fibroblast proliferation and migration inhibitor via inhibiting the ERK signaling pathway. |
format | Online Article Text |
id | pubmed-6048932 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-60489322018-08-13 Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration Zhang, Lu-Lu Du, Jun-Bao Tang, Chao-Shu Jin, Hong-Fang Huang, Ya-Qian Chin Med J (Engl) Original Article BACKGROUND: Myocardial fibrosis is an important pathological change in many heart diseases, but its pathogenesis is very complex and has not yet been fully elucidated. The study was designed to examine whether endogenous sulfur dioxide (SO(2)) is a novel myocardial fibroblast proliferation and migration inhibitor. METHODS: Primary rat myocardial fibroblasts were isolated and transfected with aspartate aminotransferase (AAT1 and AAT2) knockdown lentivirus or empty lentivirus. SO(2) content in the supernatant was determined with high-performance liquid chromatography, and the expressions of AAT1, AAT2, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated protein kinase (p-ERK), and total ERK (T-ERK) in the cells were detected. Cell migration was detected by wound healing test. Independent sample t-test (for two groups) and one-way analysis of variance (three or more groups) were used to analyze the results. RESULTS: Both AAT1 and AAT2 knockdown significantly reduced SO(2) levels (F = 31.46, P < 0.01) and AAT1/2 protein expression (AAT1, t = 12.67, P < 0.01; AAT2, t = 9.61, P < 0.01), but increased PCNA expression and Cell Counting Kit-8 (CCK-8) activity as well as the migration in rat primary myocardial fibroblasts (P < 0.01). Supplementation of SO(2) rather than pyruvate significantly inhibited the increase in proliferation and migration caused by AAT knockdown (P < 0.01). Mechanistically, the ratio of p-ERK to T-ERK was significantly increased in the AAT1/2 knockdown groups compared with that in the empty lentivirus group (AAT1, t = −7.36, P < 0.01; AAT2, t = −10.97, P < 0.01). Whereas PD98059, an inhibitor of ERK activation, successfully blocked AAT knockdown-induced PCNA upregulation (F = 74.01, P > 0.05), CCK-8 activation (F = 50.14, P > 0.05), and migration augmentation in myocardial fibroblasts (24 h, F = 37.08, P > 0.05; 48 h, F = 58.60, P > 0.05). CONCLUSION: Endogenous SO(2) might be a novel myocardial fibroblast proliferation and migration inhibitor via inhibiting the ERK signaling pathway. Medknow Publications & Media Pvt Ltd 2018-07-20 /pmc/articles/PMC6048932/ /pubmed/29998892 http://dx.doi.org/10.4103/0366-6999.235875 Text en Copyright: © 2018 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Zhang, Lu-Lu Du, Jun-Bao Tang, Chao-Shu Jin, Hong-Fang Huang, Ya-Qian Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration |
title | Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration |
title_full | Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration |
title_fullStr | Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration |
title_full_unstemmed | Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration |
title_short | Inhibitory Effects of Sulfur Dioxide on Rat Myocardial Fibroblast Proliferation and Migration |
title_sort | inhibitory effects of sulfur dioxide on rat myocardial fibroblast proliferation and migration |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048932/ https://www.ncbi.nlm.nih.gov/pubmed/29998892 http://dx.doi.org/10.4103/0366-6999.235875 |
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