PTEN enhances nasal epithelial cell resistance to TNFα‑induced inflammatory injury by limiting mitophagy via repression of the TLR4‑JNK‑Bnip3 pathway

  • Authors:
    • Meng Li
    • Xiang Yang
    • Shouchuan Wang
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  • Published online on: July 9, 2018     https://doi.org/10.3892/mmr.2018.9264
  • Pages: 2973-2986
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Abstract

Nasal epithelial cell inflammatory injury is associated with chronic obstructive pulmonary disease development. However, the mechanism by which inflammation triggers nasal epithelial cell damage remains unclear. In the present study, tumor necrosis factor (TNF)α was used to induce an inflammatory injury and explore the underlying pathogenesis for nasal epithelial cell apoptosis in vitro, with a focus on mitochondrial homeostasis. Then, cellular apoptosis was detected via a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay and western blotting. Mitochondrial function was evaluated via JC‑1 staining, mPTP opening measurement and western blotting. The results demonstrated that TNFα treatment induced nasal epithelial cell apoptosis, proliferation arrest and migration inhibition via downregulating phosphatase and tensin homolog (PTEN) levels. Increased PTEN expression was associated with reduce Toll‑like receptor (TLR)4‑c‑Jun kinase (JNK)‑Bcl2‑interacting protein 3 (Bnip3) pathway signaling, leading to reductions in mitophagy activity. Excessive mitophagy resulted in ATP deficiencies, mitochondrial dysfunction, caspase‑9 activation and cellular apoptosis. By contrast, PTEN overexpression in nasal epithelial cells alleviated the mitochondrial damage and cellular apoptosis via inhibiting the TLR4‑JNK‑Bnip3 pathway, favoring the survival of nasal epithelial cells under inflammatory injury. Therefore, this data uncovered a potential molecular basis for nasal epithelial cell apoptosis in response to inflammatory injury, and PTEN was identified as the endogenous defender of nasal epithelial cell survival via controlling lethal mitophagy by inhibiting the TLR4‑JNK‑Bnip3 pathway, suggesting that this pathway may be a potential target for clinically treating chronic nasal and sinus inflammatory injury.
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September-2018
Volume 18 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li M, Yang X and Wang S: PTEN enhances nasal epithelial cell resistance to TNFα‑induced inflammatory injury by limiting mitophagy via repression of the TLR4‑JNK‑Bnip3 pathway. Mol Med Rep 18: 2973-2986, 2018.
APA
Li, M., Yang, X., & Wang, S. (2018). PTEN enhances nasal epithelial cell resistance to TNFα‑induced inflammatory injury by limiting mitophagy via repression of the TLR4‑JNK‑Bnip3 pathway. Molecular Medicine Reports, 18, 2973-2986. https://doi.org/10.3892/mmr.2018.9264
MLA
Li, M., Yang, X., Wang, S."PTEN enhances nasal epithelial cell resistance to TNFα‑induced inflammatory injury by limiting mitophagy via repression of the TLR4‑JNK‑Bnip3 pathway". Molecular Medicine Reports 18.3 (2018): 2973-2986.
Chicago
Li, M., Yang, X., Wang, S."PTEN enhances nasal epithelial cell resistance to TNFα‑induced inflammatory injury by limiting mitophagy via repression of the TLR4‑JNK‑Bnip3 pathway". Molecular Medicine Reports 18, no. 3 (2018): 2973-2986. https://doi.org/10.3892/mmr.2018.9264