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Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation
Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant properties, and has received extensive attention in anti-atherosclerosis. Yet little is known about apoA-I ’s role in peritoneal dialysis. In...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10422021/ https://www.ncbi.nlm.nih.gov/pubmed/37576813 http://dx.doi.org/10.3389/fphar.2023.1106339 |
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author | Lu, Jing Gao, Jie Sun, Jing Wang, Haiping Sun, Huijuan Huang, Qian Zhang, Yao Zhong, Shuo |
author_facet | Lu, Jing Gao, Jie Sun, Jing Wang, Haiping Sun, Huijuan Huang, Qian Zhang, Yao Zhong, Shuo |
author_sort | Lu, Jing |
collection | PubMed |
description | Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant properties, and has received extensive attention in anti-atherosclerosis. Yet little is known about apoA-I ’s role in peritoneal dialysis. In this study, by analyzing PD patients (n = 81), we found that decreased apoA/HDL-C ratio is significantly associated with rapid decline in peritoneal function. Further studies were performed in animal experiments to determine the ascendancy of apolipoprotein A-I mimetic peptide (D-4F) on peritoneum, we found that D-4F administration reduced peritoneal fibrosis and peritoneal endothelial mesenchymal transformation (EMT) induced by high glucose peritoneal dialysate, such as N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA) expression decreased. In mechanism, D-4F can significantly inhibit Smad2/3 phosphorylation, which is the major pathway leading to fibrosis. Furthermore, D-4F treatment inhibited NADPH oxidase and thiobarbituric acid reactive substances (TBARS) expression, increased the activity of certain enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Finally, treatment with D-4F inhibits the expression of interleukins-6(IL-6), Interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Taken together, based on the above research evidence, apoA-I and its peptide mimic may regulate the oxidative stress, TGF- β1/Smads signaling pathway and inflammatory response to reduce peritoneal fibrosis due to peritoneal dialysis. |
format | Online Article Text |
id | pubmed-10422021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104220212023-08-13 Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation Lu, Jing Gao, Jie Sun, Jing Wang, Haiping Sun, Huijuan Huang, Qian Zhang, Yao Zhong, Shuo Front Pharmacol Pharmacology Apolipoprotein A-I (apoA-I), 90% of which is present in high-density lipoprotein (HDL), is the main constituent of HDL, has anti-inflammatory and anti-oxidant properties, and has received extensive attention in anti-atherosclerosis. Yet little is known about apoA-I ’s role in peritoneal dialysis. In this study, by analyzing PD patients (n = 81), we found that decreased apoA/HDL-C ratio is significantly associated with rapid decline in peritoneal function. Further studies were performed in animal experiments to determine the ascendancy of apolipoprotein A-I mimetic peptide (D-4F) on peritoneum, we found that D-4F administration reduced peritoneal fibrosis and peritoneal endothelial mesenchymal transformation (EMT) induced by high glucose peritoneal dialysate, such as N-cadherin, Fibronectin, Vimentin, and α-smooth muscle actin (α-SMA) expression decreased. In mechanism, D-4F can significantly inhibit Smad2/3 phosphorylation, which is the major pathway leading to fibrosis. Furthermore, D-4F treatment inhibited NADPH oxidase and thiobarbituric acid reactive substances (TBARS) expression, increased the activity of certain enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Finally, treatment with D-4F inhibits the expression of interleukins-6(IL-6), Interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Taken together, based on the above research evidence, apoA-I and its peptide mimic may regulate the oxidative stress, TGF- β1/Smads signaling pathway and inflammatory response to reduce peritoneal fibrosis due to peritoneal dialysis. Frontiers Media S.A. 2023-07-28 /pmc/articles/PMC10422021/ /pubmed/37576813 http://dx.doi.org/10.3389/fphar.2023.1106339 Text en Copyright © 2023 Lu, Gao, Sun, Wang, Sun, Huang, Zhang and Zhong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Lu, Jing Gao, Jie Sun, Jing Wang, Haiping Sun, Huijuan Huang, Qian Zhang, Yao Zhong, Shuo Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation |
title | Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation |
title_full | Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation |
title_fullStr | Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation |
title_full_unstemmed | Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation |
title_short | Apolipoprotein A-I attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation |
title_sort | apolipoprotein a-i attenuates peritoneal fibrosis associated with peritoneal dialysis by inhibiting oxidative stress and inflammation |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10422021/ https://www.ncbi.nlm.nih.gov/pubmed/37576813 http://dx.doi.org/10.3389/fphar.2023.1106339 |
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