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Alpha-enolase regulates the malignant phenotype of pulmonary artery smooth muscle cells via the AMPK-Akt pathway

Author

Listed:
  • Jingbo Dai

    (University of Illinois at Chicago)

  • Qiyuan Zhou

    (University of Illinois at Chicago)

  • Jiwang Chen

    (University of Illinois at Chicago)

  • Megan L. Rexius-Hall

    (University of Illinois at Chicago)

  • Jalees Rehman

    (University of Illinois at Chicago
    University of Illinois at Chicago
    University of Illinois at Chicago)

  • Guofei Zhou

    (University of Illinois at Chicago
    The First Affiliated Hospital of Guangzhou Medical University, Guangzhou)

Abstract

The molecular mechanisms underlying the metabolic shift toward increased glycolysis observed in pulmonary artery smooth muscle cells (PASMC) during the pathogenesis of pulmonary arterial hypertension (PAH) are not fully understood. Here we show that the glycolytic enzyme α-enolase (ENO1) regulates the metabolic reprogramming and malignant phenotype of PASMC. We show that ENO1 levels are elevated in patients with associated PAH and in animal models of hypoxic pulmonary hypertension (HPH). The silencing or inhibition of ENO1 decreases PASMC proliferation and de-differentiation, and induces PASMC apoptosis, whereas the overexpression of ENO1 promotes a synthetic, de- differentiated, and apoptotic-resistant phenotype via the AMPK-Akt pathway. The suppression of ENO1 prevents the hypoxia-induced metabolic shift from mitochondrial respiration to glycolysis in PASMC. Finally, we find that pharmacological inhibition of ENO1 reverses HPH in mice and rats, suggesting ENO1 as a regulator of pathogenic metabolic reprogramming in HPH.

Suggested Citation

  • Jingbo Dai & Qiyuan Zhou & Jiwang Chen & Megan L. Rexius-Hall & Jalees Rehman & Guofei Zhou, 2018. "Alpha-enolase regulates the malignant phenotype of pulmonary artery smooth muscle cells via the AMPK-Akt pathway," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06376-x
    DOI: 10.1038/s41467-018-06376-x
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