The role of BFGF-related transcriptional regulation and alternative polyadenylation in calcification model of valve interstitial cells induced by osteoblastic medium

Abstract

Abstract Objective Calcific aortic valve disease (CAVD) is a major cause of aortic stenosis resulting in angina, heart failure, and death. However, the molecular mechanism of its progression, especially the sophisticated disease-related transcriptional regulation machinery remains to be further elucidated. Methods This study was modeled on porcine valvular interstitial cells (PVIC). We used OIM to induce calcification and bFGF treatment to inhibit calcification. The mRNA expression profile of PVICs and their related transcriptional regulation were investigated using transcriptome sequencing. We used DaPars to further examine alternative polyadenylation (APA) among the different treatment groups. Results We identified global APA alteration in the OIM, OIM-bFGF, and Ctrl treatment groups. We also identified the CAT gene as one of the crucial candidate genes that may contribute to calcification inhibition through APA regulation. The alteration of both APA and protein levels of the CAT gene in the bFGF-treated group was further validated using qRT-PCR and western blotting analysis. Conclusion We described a global APA change in a calcification model related to CAVD. We revealed that transcriptional regulation of the CAT gene may contribute to bFGF-induced calcification inhibition.