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Decrease in Tripartite Motif Containing 24 suppresses hypoxia-induced proliferation and migration of pulmonary

Jingwen Xu1, Yujia Zhong1, Zhang Wang1

  • 1Department of Geriatrics, The General Hospital of Western Theater Command, Chengdu, P.R. China.

Bioengineered
|June 2, 2022
PubMed

Insights

Tripartite Motif Containing 24 (TRIM24) drives pulmonary artery smooth muscle cell proliferation and migration in pulmonary arterial hypertension. Silencing TRIM24 inhibits this process by affecting the AKT/mTORC1 pathway.

Area of Science:

  • Cardiovascular Biology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Tripartite Motif Containing 24 (TRIM24) is an oncogenic protein implicated in cancer cell proliferation.
  • The specific role of TRIM24 in pulmonary artery smooth muscle cell (PASMC) proliferation and migration, particularly in the context of pulmonary arterial hypertension (PAH), is not well understood.

Purpose of the Study:

  • To investigate the role of TRIM24 in PASMC proliferation and migration during the development of pulmonary arterial hypertension (PAH).
  • To elucidate the underlying molecular mechanisms involving the AKT/mTORC1 signaling pathway.

Main Methods:

  • Assessed TRIM24 expression in pulmonary arteries of chronic hypoxia-induced PAH (CH-PAH) mice and hypoxia-challenged PASMCs.
  • Utilized TRIM24 silencing via short hairpin RNA (shTrim24) to evaluate effects on PASMC proliferation (Ki-67) and migration (wound-healing).
  • Examined the phosphorylation status of AKT, S6, and 4EBP1 (mTORC1 effectors) and manipulated AKT/mTORC1 signaling to assess rescue effects.

Main Results:

  • TRIM24 expression was upregulated in PAs of CH-PAH mice and hypoxia-treated PASMCs.
  • TRIM24 silencing significantly suppressed hypoxia-induced PASMC proliferation and migration.
  • Hypoxia-induced AKT/mTORC1 pathway activation was attenuated by TRIM24 silencing, and pathway restoration reversed the inhibitory effects of TRIM24 knockdown.

Conclusions:

  • TRIM24 plays a critical role in the excessive proliferation and migration of PASMCs under hypoxic conditions relevant to PAH.
  • TRIM24 promotes PASMC proliferation and migration, at least partly, by enhancing the activity of the AKT/mTORC1 signaling pathway.
Keywords:
AKTTRIM24mTORC1pulmonary arterial hypertensionpulmonary artery smooth muscle cells

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