Cargando…
Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway
BACKGROUND: Myocardial fibrosis is an important factor in the induction and maintenance of atrial fibrillation (AF). Fibromodulin (FMOD) promotes fibrotic gene expression. However, its specific role in spontaneously hypertensive rats (SHR)‐AF remains unclear. METHODS: We analyzed FMOD mRNA and prote...
Autores principales: | , , , |
---|---|
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/PMC10604567/ https://www.ncbi.nlm.nih.gov/pubmed/37904680 http://dx.doi.org/10.1002/iid3.1003 |
_version_ | 1785126865624629248 |
---|---|
author | Liang, Yuming Zhou, Yun Wang, Jialin He, Yan |
author_facet | Liang, Yuming Zhou, Yun Wang, Jialin He, Yan |
author_sort | Liang, Yuming |
collection | PubMed |
description | BACKGROUND: Myocardial fibrosis is an important factor in the induction and maintenance of atrial fibrillation (AF). Fibromodulin (FMOD) promotes fibrotic gene expression. However, its specific role in spontaneously hypertensive rats (SHR)‐AF remains unclear. METHODS: We analyzed FMOD mRNA and protein expression in rat atrial tissues using RT‐qPCR, Western blot analysis, and immunohistochemistry. Histopathological examination of atrial tissues was performed using hematoxylin and eosin (H&E), Masson's trichrome, and Picrosirius red staining. The levels of inflammatory and fibrosis‐related proteins were measured using Western blot analysis. RESULTS: FMOD relative mRNA and protein expression levels were notably upregulated in atrial tissues of both AF groups (normal‐AF and SHR‐AF groups) than that in atrial tissues of the no‐AF group (normal and SHR group). This effect was particularly pronounced in the SHR‐AF group. Pathological changes revealed that the extracellular matrix, collagen, collagen fibers, and left atrial diameter were notably increased in the atrial tissues from the SHR‐AF group compared to those in the atrial tissues from the SHR group, whereas the left ventricular fractional shortening and left ventricular ejection fraction were notably lower. Expression of TLR4, MyD88, NLRP3, TGF‐β1, collagen I, and collagen II mRNA were clearly higher in atrial tissues from the SHR‐AF group than in those from the SHR group. Protein levels of TLR4, MyD88, NLRP3, Cleavage‐Caspase‐1, Cleavage‐IL‐1β, TGF‐β1, p‐Smad2, collagen I, and collagen II were clearly higher in atrial tissues from the SHR‐AF group than in those from the SHR group. FMOD knockdown inhibited atrial fibrosis, collagen accumulation, and the TLR4/MyD88/NLRP3 signaling pathway. CONCLUSION: Downregulation of FMOD attenuated inflammatory signaling and atrial fibrosis in SHR‐AF by inhibiting the TLR4/NLRP3 signaling pathway. Therefore, FMOD may be a promising therapeutic target in AF. |
format | Online Article Text |
id | pubmed-10604567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106045672023-10-28 Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway Liang, Yuming Zhou, Yun Wang, Jialin He, Yan Immun Inflamm Dis Original Articles BACKGROUND: Myocardial fibrosis is an important factor in the induction and maintenance of atrial fibrillation (AF). Fibromodulin (FMOD) promotes fibrotic gene expression. However, its specific role in spontaneously hypertensive rats (SHR)‐AF remains unclear. METHODS: We analyzed FMOD mRNA and protein expression in rat atrial tissues using RT‐qPCR, Western blot analysis, and immunohistochemistry. Histopathological examination of atrial tissues was performed using hematoxylin and eosin (H&E), Masson's trichrome, and Picrosirius red staining. The levels of inflammatory and fibrosis‐related proteins were measured using Western blot analysis. RESULTS: FMOD relative mRNA and protein expression levels were notably upregulated in atrial tissues of both AF groups (normal‐AF and SHR‐AF groups) than that in atrial tissues of the no‐AF group (normal and SHR group). This effect was particularly pronounced in the SHR‐AF group. Pathological changes revealed that the extracellular matrix, collagen, collagen fibers, and left atrial diameter were notably increased in the atrial tissues from the SHR‐AF group compared to those in the atrial tissues from the SHR group, whereas the left ventricular fractional shortening and left ventricular ejection fraction were notably lower. Expression of TLR4, MyD88, NLRP3, TGF‐β1, collagen I, and collagen II mRNA were clearly higher in atrial tissues from the SHR‐AF group than in those from the SHR group. Protein levels of TLR4, MyD88, NLRP3, Cleavage‐Caspase‐1, Cleavage‐IL‐1β, TGF‐β1, p‐Smad2, collagen I, and collagen II were clearly higher in atrial tissues from the SHR‐AF group than in those from the SHR group. FMOD knockdown inhibited atrial fibrosis, collagen accumulation, and the TLR4/MyD88/NLRP3 signaling pathway. CONCLUSION: Downregulation of FMOD attenuated inflammatory signaling and atrial fibrosis in SHR‐AF by inhibiting the TLR4/NLRP3 signaling pathway. Therefore, FMOD may be a promising therapeutic target in AF. John Wiley and Sons Inc. 2023-10-27 /pmc/articles/PMC10604567/ /pubmed/37904680 http://dx.doi.org/10.1002/iid3.1003 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 Liang, Yuming Zhou, Yun Wang, Jialin He, Yan Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway |
title | Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway |
title_full | Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway |
title_fullStr | Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway |
title_full_unstemmed | Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway |
title_short | Downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting TLR4/NLRP3 signaling pathway |
title_sort | downregulation of fibromodulin attenuates inflammatory signaling and atrial fibrosis in spontaneously hypertensive rats with atrial fibrillation via inhibiting tlr4/nlrp3 signaling pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604567/ https://www.ncbi.nlm.nih.gov/pubmed/37904680 http://dx.doi.org/10.1002/iid3.1003 |
work_keys_str_mv | AT liangyuming downregulationoffibromodulinattenuatesinflammatorysignalingandatrialfibrosisinspontaneouslyhypertensiveratswithatrialfibrillationviainhibitingtlr4nlrp3signalingpathway AT zhouyun downregulationoffibromodulinattenuatesinflammatorysignalingandatrialfibrosisinspontaneouslyhypertensiveratswithatrialfibrillationviainhibitingtlr4nlrp3signalingpathway AT wangjialin downregulationoffibromodulinattenuatesinflammatorysignalingandatrialfibrosisinspontaneouslyhypertensiveratswithatrialfibrillationviainhibitingtlr4nlrp3signalingpathway AT heyan downregulationoffibromodulinattenuatesinflammatorysignalingandatrialfibrosisinspontaneouslyhypertensiveratswithatrialfibrillationviainhibitingtlr4nlrp3signalingpathway |