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NLRC3 inhibits PDGF-induced PASMCs proliferation via PI3K-mTOR pathway

Li-Huang Zha1, Jun Zhou2, Yilong Tan3

  • 1Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Journal of Cellular Physiology
|May 9, 2020
PubMed

Insights

Nucleotide-oligomerization domain-like receptor C3 (NLRC3) inhibits pulmonary artery smooth muscle cell proliferation. NLRC3 suppresses the PI3K-mTOR pathway, offering protection against abnormal cell growth.

Area of Science:

  • Cell Biology
  • Immunology
  • Physiology

Background:

  • Pulmonary artery smooth muscle cells (PASMCs) proliferation is implicated in pulmonary hypertension.
  • The role of nucleotide-oligomerization domain-like receptor subfamily C3 (NLRC3) in PASMCs is largely unexplored.
  • Platelet-derived growth factor (PDGF) is a known mitogen for PASMCs.

Purpose of the Study:

  • To investigate the function of NLRC3 in PDGF-induced PASMC proliferation.
  • To elucidate the underlying molecular mechanisms involving the PI3K-mTOR pathway.

Main Methods:

  • PASMC culture and stimulation with PDGF.
  • Overexpression and knockdown of NLRC3.
  • Inhibition of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways.
  • Western blot analysis to assess protein phosphorylation.

Main Results:

  • PDGF-induced PASMC proliferation was attenuated by PI3K or mTOR inhibitors.
  • NLRC3 overexpression inhibited PASMC proliferation and PI3K/mTOR phosphorylation.
  • NLRC3 knockdown reversed these inhibitory effects.
  • Targeting PI3K or mTOR modulated NLRC3's effects.
  • PI3K activation correlated with mTOR phosphorylation.

Conclusions:

  • PDGF induces abnormal PASMC proliferation.
  • NLRC3 acts as a suppressor of the PI3K-mTOR signaling pathway.
  • NLRC3 inhibits PASMC proliferation, suggesting a protective role against pulmonary hypertension pathogenesis.
Keywords:
NLRC3PASMCsPI3KmTORproliferation

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