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Smurf1 regulates macrophage proliferation, apoptosis and migration via JNK and p38 MAPK signaling pathways

Jing Guo1, Xiao Qiu2, Luo Zhang3

  • 1Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Beijing, 100021, China; Department of Inorganic Non-metallic Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China.

Molecular Immunology
|March 19, 2018
PubMed

Insights

Smad ubiquitylation regulatory factor 1 (Smurf1) promotes macrophage proliferation and apoptosis while inhibiting migration. Its depletion upregulates JNK and p38 MAPK signaling, affecting these cellular processes.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Smad ubiquitylation regulatory factor 1 (Smurf1) is known for its roles in bone homeostasis, development, cell cycle, and tumorigenesis.
  • The specific functions of Smurf1 in macrophage proliferation, apoptosis, and migration remain largely uncharacterized.

Purpose of the Study:

  • To investigate the role of Smurf1 in regulating macrophage proliferation, apoptosis, and migration.
  • To elucidate the underlying molecular mechanisms involving JNK and p38 MAPK signaling pathways.

Main Methods:

  • Smurf1 expression analysis in LPS-induced RAW264.7 macrophages and mouse embryonic fibroblasts (MEFs).
  • Smurf1 knockdown experiments to assess effects on macrophage proliferation, apoptosis, and migration.
  • Analysis of JNK and p38 MAPK signaling pathway activation in Smurf1-depleted cells.

Main Results:

  • Smurf1 expression was elevated in LPS-induced macrophages and MEFs.
  • Knockdown of Smurf1 suppressed macrophage proliferation but enhanced apoptosis and migration.
  • Smurf1 depletion led to the upregulation of JNK and p38 MAPK signaling.
  • Inhibition of JNK and p38 MAPK pathways rescued the observed phenotypes in Smurf1 knockdown cells.

Conclusions:

  • Smurf1 acts as a positive regulator of macrophage proliferation and apoptosis.
  • Smurf1 functions as a negative regulator of macrophage migration.
  • The JNK and p38 MAPK pathways are critical mediators of Smurf1's effects on macrophage behavior.
Keywords:
ApoptosisJNK and p38 signalingMacrophageMigrationProliferationSmurf1

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