Anti-fibrotic mechanism of SPP1 knockdown in atrial fibrosis associates with inhibited mitochondrial DNA damage and TGF-β/SREBP2/PCSK9 signaling.

ABSTRACT: Atrial fibrosis occurs frequently with structural heart disease and is considered as a major cause of arrhythmia. Microarray-based profiling predicted the differential expression of SPP1 in atrial fibrosis. Herein, we aimed to analyze the role of shRNA-mediated SPP1 knockdown in the progression of atrial fibrosis as well as the downstream mechanism. In vivo model in mice and in vitro HL-1 cell model of atrial fibrosis were developed by the angiotensin II (Ang II) method, where SPP1 expression was validated by RT-qPCR. Gain- and loss-of-function experiments were performed in Ang II-induced mice and HL-1 cells to evaluate the effect of the SPP1/TGF-β/SREBP2/PCSK9 axis on cell viability, apoptosis, collagen production and mitochondrial DNA (mtDNA) damage in atrial fibrosis. Expression of SPP1

SUBMITTER: Du X 

PROVIDER: S-EPMC9068627 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature