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SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy

Yu Ren1, Yun Wu2,3, Wenshuai He2,3

  • 1Scientific Research Department, Inner Mongolia People's Hospital, Inner Mongolia Autonomous Region, Hohhot, 010017, China.

Open Medicine (Warsaw, Poland)
|July 19, 2023
PubMed

Insights

Secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2) promotes heart failure (HF) by affecting autophagy and the TGF-β1/Smad3 pathway. Reducing SMOC2 improves cardiac function in HF models.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Heart failure (HF) is a significant global health burden.
  • Understanding the molecular mechanisms underlying HF is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of secreted protein acidic and rich in cysteine-related modular calcium-binding protein 2 (SMOC2) in the development of heart failure.
  • To elucidate the underlying mechanisms involving autophagy and the TGF-β1/Smad3 signaling pathway.

Main Methods:

  • Established a rat model of heart failure.
  • Examined SMOC2 expression and performed SMOC2 knockdown via transfection.
  • Assessed cardiac function and damage.
  • Evaluated autophagy markers (LC3-II/I, Beclin-1, p62) and the TGF-β1/Smad3 pathway.
  • Utilized transmission electron microscopy to observe autophagosomes.
  • Administered a TGF-β agonist (SRI-011381) to explore pathway interactions.

Main Results:

  • SMOC2 expression was significantly elevated in the heart failure rat model.
  • Downregulation of SMOC2 improved cardiac function and reduced cardiac damage.
  • SMOC2 knockdown normalized autophagy-related molecule levels and autophagosome formation.
  • SMOC2 downregulation inhibited the TGF-β1/Smad3 signaling pathway, an effect reversed by SRI-011381.

Conclusions:

  • SMOC2 plays a critical role in promoting heart failure development.
  • SMOC2 knockdown exerts protective effects by modulating TGF-β1/Smad3 signaling-mediated autophagy.
  • SMOC2 represents a potential therapeutic target for heart failure treatment.
Keywords:
SMOC2TGF-β1/Smad3 signaling pathwayautophagyheart failure

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