ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis

Shen，Mingkui1; Li，Kuankuan1; Wang，Lulu2; Feng，Li2; Zhang，Xinyu1; Zhang，Haoping1; Zhou，Honggang1; Pei，Guoxian2

2024

10.18632/aging.205412

Aging   影响因子和分区

1945-4589

Background: Extracellular matrix metabolism dysregulation in nucleus pulposus (NP) cells represents a crucial pathophysiological feature of intervertebral disc degeneration (IDD). Our study elucidates the role and mechanism of Testis expressed 11 (TEX11, also called ZIP4) extracellular matrix degradation in the NP. Materials and methods: Interleukin-1β (IL-1β) and H2O2 were used to treat NP cells to establish an IDD cell model. Normal NP tissues and NP tissues from IDD patients were harvested. ZIP4 mRNA and protein profiles in NP cells and tissues were examined. Enzyme-linked immunosorbent assay (ELISA) confirmed the profiles of TNF-α, IL-6, MDA, and SOD in NP cells. The alterations of reactive oxygen species (ROS), lactate dehydrogenase (LDH), COX2, iNOS, MMP-3, MMP-13, collagen II, aggrecan, FoxO3a, histone deacetylase 4 (HDAC4), Sirt1 and NF-κB levels in NP cells were determined using different assays. Results: The ZIP4 profile increased in the NP tissues of IDD patients and IL-1β- or H2O2-treated NP cells. ZIP4 upregulation bolstered inflammation and oxidative stress in NP cells undergoing IL-1β treatment and exacerbated their extracellular matrix degradation, whereas ZIP4 knockdown produced the opposite outcome. Mechanistically, ZIP4 upregulated HDAC4 and enhanced NF-κB phosphorylation while repressing Sirt1 and FoxO3a phosphorylation levels. HDAC4 knockdown or Sirt1 promotion attenuated the effects mediated by ZIP4 overexpression in NP cells. Conclusions: ZIP4 upregulation aggravates the extracellular matrix (ECM) degradation of NP cells by mediating inflammation and oxidative stress through the HDAC4-FoxO3a axis.

extracellular matrix degradation FoxO3a HDAC4 nucleus pulposus cells ZIP4

SCI

英语

其他

Science and Technology joint project of Henan Provincial Health Commission[LHGJ20190859] ; Overseas Research and Training Project of Health Science and Technology Talents in Henan Province[HWYX 2019159]

Cell Biology ; Geriatrics & Gerontology

Cell Biology ; Geriatrics & Gerontology

WOS:001167149500036

IMPACT JOURNALS LLC

2-s2.0-85183203898

Scopus

1.Intervertebral Disc Center,Third Hospital of Henan Province,Zhengzhou,Henan,450006,China
2.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Shen，Mingkui,Li，Kuankuan,Wang，Lulu,et al. ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis[J]. Aging,2024,16(1):685-700.

Shen，Mingkui.,Li，Kuankuan.,Wang，Lulu.,Feng，Li.,Zhang，Xinyu.,...&Pei，Guoxian.(2024).ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis.Aging,16(1),685-700.

Shen，Mingkui,et al."ZIP4 upregulation aggravates nucleus pulposus cell degradation by promoting inflammation and oxidative stress by mediating the HDAC4-FoxO3a axis".Aging 16.1(2024):685-700.