Though vascular smooth muscle cell (VSMC) proliferation underlies all cardiovascular hyperplastic disorders, our understanding of the molecular mechanisms responsible for this cellular process is still incomplete. Here we report that SRSF1 (serine/arginine-rich splicing factor 1), an essential splicing factor, promotes VSMC proliferation and injury-induced neointima formation. Vascular injury in vivo and proliferative stimuli in vitro stimulate SRSF1 expression. Mice lacking SRSF1 specifically in SMCs develop less intimal thickening after wire injury. Expression of SRSF1 in rat arteries enhances neointima formation. SRSF1 overexpression increases, while SRSF1 knockdown suppresses the proliferation and migration of cultured human aortic and coronary arterial SMCs. Mechanistically, SRSF1 favours the induction of a truncated p53 isoform, Δ133p53, which has an equal proliferative effect and in turn transcriptionally activates Krüppel-like factor 5 (KLF5) via the Δ133p53-EGR1 complex, resulting in an accelerated cell-cycle progression and increased VSMC proliferation. Our study provides a potential therapeutic target for vascular hyperplastic disease.

中文翻译：

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SRSF1通过Δ133p53/ EGR1 / KLF5途径促进血管平滑肌细胞增殖。

尽管血管平滑肌细胞（VSMC）增殖是所有心血管增生性疾病的根本原因，但我们对造成这种细胞过程的分子机制的理解仍不完全。在这里我们报告说，SRSF1（富含丝氨酸/精氨酸的剪接因子1），一种必要的剪接因子，促进了VSMC增殖和损伤诱导的新内膜形成。体内血管损伤和体外增殖刺激刺激SRSF1表达。SMC中缺少SRSF1的小鼠在导线损伤后内膜增厚的可能性降低。SRSF1在大鼠动脉中的表达增强了新内膜的形成。SRSF1过表达增加，而SRSF1敲低抑制培养的人主动脉和冠状动脉SMC的增殖和迁移。从机理上讲，SRSF1有助于诱导截短的p53亚型Δ133p53，具有同等的增殖作用，并通过Δ133p53-EGR1复合物转录激活Krüppel样因子5（KLF5），从而加快细胞周期进程并增加VSMC增殖。我们的研究为血管增生性疾病提供了潜在的治疗靶点。