Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells

  • Authors:
    • Yuwei Zhang
    • Yingquan Luo
    • Yina Wang
    • Hong Liu
    • Yu Yang
    • Qiong Wang
  • View Affiliations

  • Published online on: September 17, 2018     https://doi.org/10.3892/ijmm.2018.3881
  • Pages: 3467-3476
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Intermittent hypoxia/reoxygenation (IHR), characterized by repeated episodes of hypoxia interspersed with periods of reoxygenation, has been found to induce pro‑inflammatory cytokine production and is increasingly recognized as a major pathophysiological factor in various disease processes with distinct cell and molecular responses. The present study is the first, to the best of our knowledge, to investigate the effects of ubiquitin‑specific peptidase 8 (USP8) on IHR‑induced inflammation in renal tubular epithelial cells and examine the underlying mechanism. Following transfection of plasmids, HK‑2 and TCMK‑1 cells were incubated for eight cycles of IHR treatment including 3 h of hypoxic incubation followed by 3 h of normoxic culture. It was demonstrated that the expression of USP8 was decreased in IHR conditions but not in normoxic or continuous hypoxic conditions. In addition, IHR‑induced inflammation was suppressed in USP8‑overexpressinh renal tubular epithelial cells, and the silencing of USP8 markedly aggravated inflammation. Furthermore, it was found that the overexpression of USP8 inhibited the IHR‑induced activation of nuclear factor‑κB and it was demonstrated that USP8 interacted with transforming growth factor‑β‑activated kinase‑1 (TAK1) and deubiquitinated the K63‑linked ubiquitination of TAK1. Taken together, the results demonstrated the role of USP8 in IHR‑induced inflammation and suggested USP8 as a potential and specific therapeutic target for IHR‑related diseases.
View Figures
View References

Related Articles

Journal Cover

December-2018
Volume 42 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Luo Y, Wang Y, Liu H, Yang Y and Wang Q: Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells. Int J Mol Med 42: 3467-3476, 2018
APA
Zhang, Y., Luo, Y., Wang, Y., Liu, H., Yang, Y., & Wang, Q. (2018). Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells. International Journal of Molecular Medicine, 42, 3467-3476. https://doi.org/10.3892/ijmm.2018.3881
MLA
Zhang, Y., Luo, Y., Wang, Y., Liu, H., Yang, Y., Wang, Q."Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells". International Journal of Molecular Medicine 42.6 (2018): 3467-3476.
Chicago
Zhang, Y., Luo, Y., Wang, Y., Liu, H., Yang, Y., Wang, Q."Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells". International Journal of Molecular Medicine 42, no. 6 (2018): 3467-3476. https://doi.org/10.3892/ijmm.2018.3881