SRSF1 promotes vascular smooth muscle cell proliferation through a Δ133p53/EGR1/KLF5 pathway

Ning Xie1,2, Min Chen1, Rilei Dai1

  • 1Capital Institute of Pediatrics, Beijing 100020, China.

Nature Communications
|August 12, 2017
PubMed

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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