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Lipopolysaccharide Induces Human Pulmonary Micro-Vascular Endothelial Apoptosis via the YAP Signaling Pathway

Lei Yi1, Xiaoqin Huang2, Feng Guo2

  • 1Department of Orthopedics, Shanghai Fengxian Central Hospital, Branch of The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University Shanghai, China.

Frontiers in Cellular and Infection Microbiology
|November 4, 2016
PubMed

Insights

Lipopolysaccharide (LPS) triggers lung injury by inducing apoptosis in human pulmonary micro-vascular endothelial cells (HPMECs). Yes-associated protein (YAP) activation accelerates this process, suggesting YAP inhibition as a potential therapy for sepsis-induced lung injury.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Pathology

Background:

  • Gram-negative bacterial lipopolysaccharide (LPS) causes lung vascular leakage and acute lung injury (ALI) during sepsis.
  • LPS-induced apoptosis of human pulmonary micro-vascular endothelial cells (HPMECs) exacerbates hyper-permeability and ALI.
  • The intrinsic apoptotic pathway is crucial for LPS-induced endothelial cell apoptosis, with Yes-associated protein (YAP) potentially involved.

Purpose of the Study:

  • To investigate the role of YAP protein in LPS-induced HPMEC apoptosis.
  • To elucidate the molecular mechanisms by which YAP influences LPS-induced HPMEC apoptosis and ALI.
  • To assess the therapeutic potential of inhibiting YAP in sepsis-related lung injury.

Main Methods:

  • Investigated YAP activation and nuclear accumulation in HPMECs exposed to LPS.
  • Analyzed YAP translocation, phosphorylation at Y357, and interaction with transcription factor P73.
  • Utilized small interfering RNA (siRNA) to inhibit YAP and evaluated its effects on HPMEC apoptosis and downstream targets.

Main Results:

  • LPS induced YAP activation and nuclear accumulation, accelerating HPMEC apoptosis.
  • LPS increased YAP phosphorylation at Y357, promoting its translocation to the nucleus and interaction with P73.
  • YAP inhibition via siRNA suppressed LPS-induced HPMEC apoptosis and modulated P73-mediated regulation of BAX and BCL-2 expression.

Conclusions:

  • The YAP/P73/(BAX and BCL-2)/caspase-3 signaling pathway is critical in LPS-induced HPMEC apoptosis.
  • YAP activation and nuclear accumulation play a key role in the pathogenesis of sepsis-induced ALI.
  • Inhibition of YAP represents a promising therapeutic strategy for mitigating lung injury in sepsis.
Keywords:
P73Yes-associated proteinapoptosisendothelial cellslipopolysaccharide

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