Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene

Abstract Objective Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated....

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Main Authors: Jiajun Zhang, Jun Wu, Yuan Gao, Xingli Fan, Xiaohong Liu, Guanxin Zhang, Yangfeng Tang, Lin Han
Format: Article
Language:English
Published: BMC 2024-02-01
Series:BMC Cardiovascular Disorders
Subjects:
Online Access:https://doi.org/10.1186/s12872-024-03775-5
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author Jiajun Zhang
Jun Wu
Yuan Gao
Xingli Fan
Xiaohong Liu
Guanxin Zhang
Yangfeng Tang
Lin Han
author_facet Jiajun Zhang
Jun Wu
Yuan Gao
Xingli Fan
Xiaohong Liu
Guanxin Zhang
Yangfeng Tang
Lin Han
author_sort Jiajun Zhang
collection DOAJ
description Abstract Objective Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated. Methods This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups. Results We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation. Conclusion We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.
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spelling doaj.art-c82f3032d1f04148a472611488e7996e2024-03-05T17:37:28ZengBMCBMC Cardiovascular Disorders1471-22612024-02-0124111010.1186/s12872-024-03775-5Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT geneJiajun Zhang0Jun Wu1Yuan Gao2Xingli Fan3Xiaohong Liu4Guanxin Zhang5Yangfeng Tang6Lin Han7Department of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityDepartment of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityDepartment of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityDepartment of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityDepartment of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityDepartment of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityDepartment of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityDepartment of Cardiovascular Surgery, Changhai Hospital, Second Military Medical UniversityAbstract Objective Calcific aortic valve disease (CAVD) is the leading cause of angina, heart failure, and death from aortic stenosis. However, the molecular mechanisms of its progression, especially the complex disease-related transcriptional regulatory mechanisms, remain to be further elucidated. Methods This study used porcine valvular interstitial cells (PVIC) as a model. We used osteogenic induced medium (OIM) to induce calcium deposition in PVICs to calcify them, followed by basic fibroblast growth factor (bFGF) treatment to inhibit calcium deposition. Transcriptome sequencing was used to study the mRNA expression profile of PVICs and its related transcriptional regulation. We used DaPars to further examine alternative polyadenylation (APA) between different treatment groups. Results We successfully induced calcium deposition of PVICs through OIM. Subsequently, mRNA-seq was used to identify differentially expressed mRNAs for three different treatments: control, OIM-induced and OIM-induced bFGF treatment. Global APA events were identified in the OIM and bFGF treatment groups by bioinformatics analysis. Finally, it was discovered and proven that catalase (CAT) is one of the potential targets of bFGF-induced APA regulation. Conclusion We described a global APA change in a calcium deposition model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcium deposition inhibition.https://doi.org/10.1186/s12872-024-03775-5Calcific aortic valve diseaseAlternative polyadenylationCatalasebFGF
spellingShingle Jiajun Zhang
Jun Wu
Yuan Gao
Xingli Fan
Xiaohong Liu
Guanxin Zhang
Yangfeng Tang
Lin Han
Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene
BMC Cardiovascular Disorders
Calcific aortic valve disease
Alternative polyadenylation
Catalase
bFGF
title Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene
title_full Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene
title_fullStr Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene
title_full_unstemmed Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene
title_short Inhibition of valve mesenchymal stromal cell calcium deposition by bFGF through alternative polyadenylation regulation of the CAT gene
title_sort inhibition of valve mesenchymal stromal cell calcium deposition by bfgf through alternative polyadenylation regulation of the cat gene
topic Calcific aortic valve disease
Alternative polyadenylation
Catalase
bFGF
url https://doi.org/10.1186/s12872-024-03775-5
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