Cargando…
TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling
Sinoatrial node fibrosis is involved in the pathogenesis of sinus sick syndrome (SSS). Transient receptor potential (TRP) subfamily M member 7 (TRPM7) is implicated in cardiac fibrosis. However, the mechanisms underlying the regulation of sinoatrial node (SAN) fibrosis in SSS by TRPM7 remain unknown...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Japan
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096742/ https://www.ncbi.nlm.nih.gov/pubmed/29511803 http://dx.doi.org/10.1007/s00380-018-1146-0 |
_version_ | 1783348164447698944 |
---|---|
author | Zhong, Hongbin Wang, Tingjun Lian, Guili Xu, Changsheng Wang, Huajun Xie, Liangdi |
author_facet | Zhong, Hongbin Wang, Tingjun Lian, Guili Xu, Changsheng Wang, Huajun Xie, Liangdi |
author_sort | Zhong, Hongbin |
collection | PubMed |
description | Sinoatrial node fibrosis is involved in the pathogenesis of sinus sick syndrome (SSS). Transient receptor potential (TRP) subfamily M member 7 (TRPM7) is implicated in cardiac fibrosis. However, the mechanisms underlying the regulation of sinoatrial node (SAN) fibrosis in SSS by TRPM7 remain unknown. The aim of this study was to investigate the role of angiotensin II (Ang II)/TRPM7/Smad pathway in the SAN fibrosis in rats with SSS. The rat SSS model was established with sodium hydroxide pinpoint pressing permeation. Forty-eight rats were randomly divided into six groups: normal control (ctrl), sham operation (sham), postoperative 1-, 2-, 3-, and 4-week SSS, respectively. The tissue explant culture method was used to culture cardiac fibroblasts (CFs) from rat SAN tissues. TRPM7 siRNA or encoding plasmids were used to knock down or overexpress TRPM7. Collagen (Col) distribution in SAN and atria was assessed using PASM–Masson staining. Ang II, Col I, and Col III levels in serum and tissues or in CFs were determined by ELISA. TRPM7, smad2 and p-smad2 levels were evaluated by real-time PCR, and/or western blot and immunohistochemistry. SAN and atria in rats of the SSS groups had more fibers and higher levels of Ang II, Col I and III than the sham rats. Similar findings were obtained for TRPM7 and pSmad2 expression. In vitro, Ang II promoted CFs collagen synthesis in a dose-dependent manner, and potentiated TRPM7 and p-Smad2 expression. TRPM7 depletion inhibited Ang II-induced p-Smad2 expression and collagen synthesis in CFs, whereas increased TRPM7 expression did the opposite. SAN fibrosis is regulated by the Ang II/TRPM7/Smad pathway in SSS, indicating that TRPM7 is a potential target for SAN fibrosis therapy in SSS. |
format | Online Article Text |
id | pubmed-6096742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Japan |
record_format | MEDLINE/PubMed |
spelling | pubmed-60967422018-08-24 TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling Zhong, Hongbin Wang, Tingjun Lian, Guili Xu, Changsheng Wang, Huajun Xie, Liangdi Heart Vessels Original Article Sinoatrial node fibrosis is involved in the pathogenesis of sinus sick syndrome (SSS). Transient receptor potential (TRP) subfamily M member 7 (TRPM7) is implicated in cardiac fibrosis. However, the mechanisms underlying the regulation of sinoatrial node (SAN) fibrosis in SSS by TRPM7 remain unknown. The aim of this study was to investigate the role of angiotensin II (Ang II)/TRPM7/Smad pathway in the SAN fibrosis in rats with SSS. The rat SSS model was established with sodium hydroxide pinpoint pressing permeation. Forty-eight rats were randomly divided into six groups: normal control (ctrl), sham operation (sham), postoperative 1-, 2-, 3-, and 4-week SSS, respectively. The tissue explant culture method was used to culture cardiac fibroblasts (CFs) from rat SAN tissues. TRPM7 siRNA or encoding plasmids were used to knock down or overexpress TRPM7. Collagen (Col) distribution in SAN and atria was assessed using PASM–Masson staining. Ang II, Col I, and Col III levels in serum and tissues or in CFs were determined by ELISA. TRPM7, smad2 and p-smad2 levels were evaluated by real-time PCR, and/or western blot and immunohistochemistry. SAN and atria in rats of the SSS groups had more fibers and higher levels of Ang II, Col I and III than the sham rats. Similar findings were obtained for TRPM7 and pSmad2 expression. In vitro, Ang II promoted CFs collagen synthesis in a dose-dependent manner, and potentiated TRPM7 and p-Smad2 expression. TRPM7 depletion inhibited Ang II-induced p-Smad2 expression and collagen synthesis in CFs, whereas increased TRPM7 expression did the opposite. SAN fibrosis is regulated by the Ang II/TRPM7/Smad pathway in SSS, indicating that TRPM7 is a potential target for SAN fibrosis therapy in SSS. Springer Japan 2018-03-06 2018 /pmc/articles/PMC6096742/ /pubmed/29511803 http://dx.doi.org/10.1007/s00380-018-1146-0 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Article Zhong, Hongbin Wang, Tingjun Lian, Guili Xu, Changsheng Wang, Huajun Xie, Liangdi TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling |
title | TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling |
title_full | TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling |
title_fullStr | TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling |
title_full_unstemmed | TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling |
title_short | TRPM7 regulates angiotensin II-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating Smad signaling |
title_sort | trpm7 regulates angiotensin ii-induced sinoatrial node fibrosis in sick sinus syndrome rats by mediating smad signaling |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096742/ https://www.ncbi.nlm.nih.gov/pubmed/29511803 http://dx.doi.org/10.1007/s00380-018-1146-0 |
work_keys_str_mv | AT zhonghongbin trpm7regulatesangiotensiniiinducedsinoatrialnodefibrosisinsicksinussyndromeratsbymediatingsmadsignaling AT wangtingjun trpm7regulatesangiotensiniiinducedsinoatrialnodefibrosisinsicksinussyndromeratsbymediatingsmadsignaling AT lianguili trpm7regulatesangiotensiniiinducedsinoatrialnodefibrosisinsicksinussyndromeratsbymediatingsmadsignaling AT xuchangsheng trpm7regulatesangiotensiniiinducedsinoatrialnodefibrosisinsicksinussyndromeratsbymediatingsmadsignaling AT wanghuajun trpm7regulatesangiotensiniiinducedsinoatrialnodefibrosisinsicksinussyndromeratsbymediatingsmadsignaling AT xieliangdi trpm7regulatesangiotensiniiinducedsinoatrialnodefibrosisinsicksinussyndromeratsbymediatingsmadsignaling |