RNA-binding motif protein 10 accelerates abdominal aortic aneurysm formation by inducing smooth muscle cell apoptosis
摘要
Abdominal aortic aneurysm (AAA) is a progressive, age-associated vascular disorder characterized by dilation of the abdominal aorta and a high risk of rupture. RNA-binding motif protein 10 (RBM10), a key regulator of mRNA alternative splicing involved in cell cycle control and apoptosis, has not previously been investigated in AAA. This study aimed to characterize the expression and functional role of RBM10 in AAA pathogenesis.
MethodsRBM10 expression in human AAA tissues was assessed by immunofluorescence. To explore its functional relevance, genome-wide transcriptomic profiling was performed in human aortic smooth muscle cells (HASMCs) transfected with RBM10 adenovirus or negative control for 24 h. The effects of RBM10 on HASMC proliferation and migration were evaluated using MTT and transwell assays, respectively. Apoptosis was quantified by flow cytometry.
ResultsRBM10 expression was significantly elevated in human AAA tissues and in an established animal model. RBM10 overexpression markedly suppressed HASMC proliferation and migration while promoting apoptosis. Flow cytometry confirmed enhanced apoptotic rates, consistent with transcriptomic analysis demonstrating activation of the p53 pathway. Upregulation and activation of p53 were validated at the protein level.
ConclusionsThese findings indicate that RBM10 contributes to AAA progression by promoting smooth muscle cell apoptosis, likely through a p53-dependent mechanism. RBM10 may represent a promising therapeutic target for preventing or slowing AAA development.