Format

Send to

Choose Destination
Int J Mol Med. 2018 Dec;42(6):3467-3476. doi: 10.3892/ijmm.2018.3881. Epub 2018 Sep 17.

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

Author information

1
Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.

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.

PMID:
30221684
DOI:
10.3892/ijmm.2018.3881
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Spandidos Publications
Loading ...
Support Center