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Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
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YAP1 exacerbates pyroptosis and senescence in nucleus pulposus cells by promoting BNIP3-mediated mitophagy

Xin Peng1, Hang-Yu Ji2, Jia-Wei Gao3

  • 1Department of Orthopedics, Henan Provincial People's Hospital, Peolple's Hospital of Zhengzhou University, Zhengzhou, China.

International Immunopharmacology
|October 23, 2024
PubMed

Insights

Yes-associated protein 1 (YAP1) exacerbates inflammation-induced pyroptosis and senescence in nucleus pulposus cells by promoting mitophagy. However, YAP1 may offer therapeutic potential for acute disc degeneration injuries.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Pathology

Background:

  • Yes-associated protein 1 (YAP1) is a key Hippo pathway effector involved in inflammation and mitochondrial function.
  • The role of YAP1 in pyroptosis and mitophagy within nucleus pulposus (NP) cells during inflammation is not fully understood.

Purpose of the Study:

  • To investigate the effect of YAP1 on lipopolysaccharide (LPS)-induced pyroptosis in NP cells.
  • To explore the underlying mechanisms involving mitophagy and inflammasome activation.

Main Methods:

  • Overexpression of YAP1 in NP cells.
  • LPS induction to simulate an inflammatory environment.
  • Assessment of pyroptosis, senescence, mitophagy (BNIP3-mediated), and inflammasome (NLRP3) activation.
  • In vivo studies using normal and annulus fibrosus punctured discs.

Main Results:

  • YAP1 expression was reduced in degenerative disc NP tissue.
  • YAP1 overexpression aggravated LPS-induced pyroptosis, senescence, and NLRP3 inflammasome activation.
  • Inhibition of BNIP3-mediated mitophagy reversed YAP1-induced pyroptosis and senescence.
  • In vivo, YAP1 overexpression accelerated normal disc degeneration but attenuated degeneration in annulus fibrosus punctured discs.
  • YAP1 overexpression upregulated TNFAIP3 and CLPP.

Conclusions:

  • YAP1 exacerbates LPS-induced pyroptosis and senescence in NP cells by promoting BNIP3-mediated mitophagy, contributing to disc degeneration.
  • YAP1 shows potential as a therapeutic agent for acute intervertebral disc degeneration (IDD) injuries due to its protective effects in specific in vivo models.
Keywords:
InflammationMitophagyNLRP3Nucleus pulposusYAP1

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