Work

Thrombospondin‐4 Regulates Lipopolysaccharide‐Induced Apoptosis and Inflammation in Nucleus Pulposus Cells via the Phosphatidylinositol 3‐Kinase/Protein Kinase B Pathway

Year: 2026

Type: article

Abstract: OBJECTIVE: This study investigated the expression profile of Thrombospondin-4 (THBS4) in intervertebral disc degeneration (IDD) and clarify its regulatory role in lipopolysaccharide (LPS)-induced apoptosis and inflammation in nucleus pulposus cells (NPCs) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. METHODS: IDD-related differentially expressed genes were screened through the integration of GeneCards and the Gene Expression Omnibus (GEO) database (GSE186542), followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore potential signaling mechanisms. An in vitro inflammatory injury model was established using LPS-stimulated NPCs. The effects of THBS4 overexpression on cell proliferation, apoptosis, inflammatory cytokine secretion, and extracellular matrix protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Additionally, the involvement of the PI3K/AKT pathway in mediating THBS4-related effects was confirmed using the PI3K inhibitor LY294002. RESULTS: Bioinformatics analysis revealed that THBS4 was significantly downregulated in IDD and was closely linked to the PI3K/AKT pathway. Functional assays demonstrated that overexpression of THBS4 markedly enhanced NPCs proliferation, suppressed apoptosis, reduced the secretion of tumour necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6, and increased the expression of IL-10, Aggrecan, and Collagen type II. These protective effects were accompanied by activation of the PI3K/AKT pathway and were significantly reversed by LY294002 treatment. CONCLUSION: THBS4 alleviated LPS-induced damage in NPCs through the activation of the PI3K/AKT pathway, exerting anti-apoptotic and anti-inflammatory effects; the specific upstream molecular mechanism of PI3K/AKT activation by THBS4 requires further investigation. These findings suggested that THBS4 may serve as a potential therapeutic target for IDD treatment.

Source: Immunity Inflammation and Disease

DOI: 10.1002/iid3.70484

Authors: Yang Shu, Chunhua Sun, Shi Chen

Institutions: Wuhan Sixth Hospital, Wuhan Puai Hospital

Language: English

Topic: Spine and Intervertebral Disc Pathology

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,300