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Updated: Feb 24, 2026

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Published on: April 21, 2023
SRSF1 promotes vascular smooth muscle cell proliferation through a Δ133p53/EGR1/KLF5 pathway
Abstract:
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.
Insights
Serine/arginine-rich splicing factor 1 (SRSF1) drives vascular smooth muscle cell proliferation and cardiovascular disease. Targeting SRSF1 offers a new therapeutic strategy for vascular hyperplastic disorders.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Biology
Background:
- Vascular smooth muscle cell (VSMC) proliferation is central to cardiovascular hyperplastic disorders.
- The precise molecular drivers of VSMC proliferation remain incompletely understood.
Purpose of the Study:
- To investigate the role of serine/arginine-rich splicing factor 1 (SRSF1) in VSMC proliferation and neointima formation.
- To elucidate the molecular mechanisms by which SRSF1 influences VSMC behavior.
Main Methods:
- Assessed SRSF1 expression in response to vascular injury and proliferative stimuli.
- Utilized SRSF1 knockout mouse models and in vitro VSMC cultures.
- Examined the impact of SRSF1 modulation on cell proliferation, migration, and gene expression.
Main Results:
- SRSF1 expression is upregulated by vascular injury and mitogens.
- SMCs lacking SRSF1 exhibit reduced neointima formation post-injury.
- SRSF1 overexpression promotes, while knockdown inhibits, VSMC proliferation and migration.
- SRSF1 promotes a truncated p53 isoform (Δ133p53), activating KLF5 via the Δ133p53-EGR1 complex, accelerating cell cycle progression.
Conclusions:
- SRSF1 is a key regulator of VSMC proliferation and neointima formation.
- The SRSF1/Δ133p53/KLF5 pathway is critical for accelerated cell-cycle progression in VSMCs.
- SRSF1 represents a potential therapeutic target for vascular hyperplastic diseases.
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