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

TL;DR

This study shows how bFGF can inhibit calcium buildup in heart valves by regulating the CAT gene through alternative polyadenylation.

Contribution

The study reveals a novel mechanism by which bFGF inhibits calcium deposition via alternative polyadenylation regulation of the CAT gene.

Findings

bFGF treatment inhibits calcium deposition in porcine valvular interstitial cells.

Alternative polyadenylation events were identified in response to bFGF treatment.

The CAT gene is a potential target of bFGF-induced APA regulation.

Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s12872-024-03775-5.

Figures