Related Experiment Video

Updated: May 21, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

IFT88/Kindlin-2 Signaling Prevents Mechanical Overloading-Induced PANoptosis of Nucleus Pulposus Cells by Activating

Kanglu Li1, Mingjue Chen2, Chao Chen1

  • 1Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

International Journal of Biological Sciences
|May 20, 2026
PubMed

Insights

PANoptosis, a new cell death pathway, drives nucleus pulposus cell death in intervertebral disc degeneration. Inhibiting ZBP1, a PANoptosis sensor, alleviates degeneration by restoring Kindlin-2 levels.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Orthopedics

Background:

  • Intervertebral disc degeneration (IDD) involves nucleus pulposus (NP) cell death, with unclear mechanisms.
  • PANoptosis, a novel cell death pattern, has an unknown role in IDD.

Purpose of the Study:

  • To investigate PANoptosis' contribution to mechanical overloading-induced NP cell death.
  • To explore the underlying mechanisms of PANoptosis in IDD.

Main Methods:

  • Evaluated PANoptosis in human degenerated IVD tissues, aged mice, and in vitro models.
  • Utilized Z-DNA-binding protein 1 (ZBP1) inhibition to assess PANoptosis' functional role.
  • Investigated the roles of Kindlin-2, forkhead box P1 (FOXP1), and intraflagellar transport 88 (IFT88) in the pathway.

Main Results:

  • PANoptosis markers were upregulated in degenerated IVDs and with mechanical overloading.
  • ZBP1 inhibition reduced NP cell death and alleviated IDD.
  • Kindlin-2 loss promoted PANoptosis by suppressing FOXP1 SUMOylation and increasing ZBP1 activity.
  • Mechanical overloading downregulated Kindlin-2 via IFT88, exacerbating PANoptosis and IDD.

Conclusions:

  • PANoptosis contributes to mechanical overloading-induced NP cell death and IDD.
  • The Kindlin-2/FOXP1 SUMOylation pathway, influenced by ciliary IFT88, protects NP cells from mechanical stress-induced PANoptosis.
  • This pathway presents a potential therapeutic target for IDD.
Keywords:
FOXP1IFT88Kindlin-2PANoptosisintervertebral discnucleus pulposus

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