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Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats

OBJECTIVE: The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase‐3β (GSK‐3β) and to provide new ideas for intervention in myocardial fibrosis. MATERIALS AND METHODS:...

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Autores principales: Li, Xing‐Xing, Wang, Yun‐Zhe, Liu, Chuang, Fu, Guo‐Wei, Li, Jun, Zhang, Jin‐Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10633815/
https://www.ncbi.nlm.nih.gov/pubmed/38018586
http://dx.doi.org/10.1002/iid3.1050
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author Li, Xing‐Xing
Wang, Yun‐Zhe
Liu, Chuang
Fu, Guo‐Wei
Li, Jun
Zhang, Jin‐Ying
author_facet Li, Xing‐Xing
Wang, Yun‐Zhe
Liu, Chuang
Fu, Guo‐Wei
Li, Jun
Zhang, Jin‐Ying
author_sort Li, Xing‐Xing
collection PubMed
description OBJECTIVE: The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase‐3β (GSK‐3β) and to provide new ideas for intervention in myocardial fibrosis. MATERIALS AND METHODS: MI model rats given BPS and cardiac fibroblasts (CFs) treated with BPS and TGF‐β. HE staining and Masson staining were used to detect the pathological changes of myocardial tissue. Fibrotic markers were detected by immunohistochemical staining. The expressions of GSK‐3β, cAMP response element binding protein (CREB), and p‐CREB were analyzed by qPCR and western blot analysis. EDU staining was used to detect the proliferation of CFs. The promoter activity of GSK‐3β was detected by luciferase assay. Chromatin immunoprecipitation assay was used to detect the binding levels of GSK‐3β promoter and Y‐box binding protein 1 (YBX1). The levels of intracellular cyclic adenosine monophosphate (cAMP) were analyzed by enzyme‐linked immunosorbent assay (ELISA). RESULTS: After operation, BPS improved myocardial fibrosis and upregulated GSK‐3β protein expression in male SD rats. BPS can down‐regulate α‐smooth muscle actin (α‐SMA) level and up‐regulate GSK‐3β protein expression in CFs after TGF‐β stimulation. Furthermore, GSK‐3β knockdown can reverse the effect of BPS on TGF‐β‐activated CFs, enhance α‐SMA expression, and promote the proliferation of CFs. BPS could regulate GSK‐3β expression by promoting the binding of GSK‐3β promoter to YBX1. BPS induced upregulation of p‐CREB and cAMP, resulting in reduced fibrosis, which was reversed by the knockdown of GSK‐3β or prostaglandin receptor (IPR) antagonists. CONCLUSION: BPS treatment increased the binding of YBX1 to the GSK‐3β promoter, and GSK‐3β protein expression was upregulated, which further caused the upregulation of p‐CREB and cAMP, and finally inhibited myocardial fibrosis.
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spelling pubmed-106338152023-11-10 Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats Li, Xing‐Xing Wang, Yun‐Zhe Liu, Chuang Fu, Guo‐Wei Li, Jun Zhang, Jin‐Ying Immun Inflamm Dis Original Articles OBJECTIVE: The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase‐3β (GSK‐3β) and to provide new ideas for intervention in myocardial fibrosis. MATERIALS AND METHODS: MI model rats given BPS and cardiac fibroblasts (CFs) treated with BPS and TGF‐β. HE staining and Masson staining were used to detect the pathological changes of myocardial tissue. Fibrotic markers were detected by immunohistochemical staining. The expressions of GSK‐3β, cAMP response element binding protein (CREB), and p‐CREB were analyzed by qPCR and western blot analysis. EDU staining was used to detect the proliferation of CFs. The promoter activity of GSK‐3β was detected by luciferase assay. Chromatin immunoprecipitation assay was used to detect the binding levels of GSK‐3β promoter and Y‐box binding protein 1 (YBX1). The levels of intracellular cyclic adenosine monophosphate (cAMP) were analyzed by enzyme‐linked immunosorbent assay (ELISA). RESULTS: After operation, BPS improved myocardial fibrosis and upregulated GSK‐3β protein expression in male SD rats. BPS can down‐regulate α‐smooth muscle actin (α‐SMA) level and up‐regulate GSK‐3β protein expression in CFs after TGF‐β stimulation. Furthermore, GSK‐3β knockdown can reverse the effect of BPS on TGF‐β‐activated CFs, enhance α‐SMA expression, and promote the proliferation of CFs. BPS could regulate GSK‐3β expression by promoting the binding of GSK‐3β promoter to YBX1. BPS induced upregulation of p‐CREB and cAMP, resulting in reduced fibrosis, which was reversed by the knockdown of GSK‐3β or prostaglandin receptor (IPR) antagonists. CONCLUSION: BPS treatment increased the binding of YBX1 to the GSK‐3β promoter, and GSK‐3β protein expression was upregulated, which further caused the upregulation of p‐CREB and cAMP, and finally inhibited myocardial fibrosis. John Wiley and Sons Inc. 2023-11-09 /pmc/articles/PMC10633815/ /pubmed/38018586 http://dx.doi.org/10.1002/iid3.1050 Text en © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Li, Xing‐Xing
Wang, Yun‐Zhe
Liu, Chuang
Fu, Guo‐Wei
Li, Jun
Zhang, Jin‐Ying
Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats
title Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats
title_full Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats
title_fullStr Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats
title_full_unstemmed Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats
title_short Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK‐3β expression in rats
title_sort beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating gsk‐3β expression in rats
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10633815/
https://www.ncbi.nlm.nih.gov/pubmed/38018586
http://dx.doi.org/10.1002/iid3.1050
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