PMID- 38161353
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240103
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 16
DP  - 2023
TI  - ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and 
      Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models.
PG  - 6361-6384
LID - 10.2147/JIR.S426439 [doi]
AB  - INTRODUCTION: The crosstalk between intervertebral disc degeneration (IVDD) and 
      type 2 diabetes mellitus (T2DM) has been investigated. However, the common 
      mechanism underlying this phenomenon has not been clearly elucidated. This study 
      aimed to explore the shared gene signatures of IVDD and T2DM. METHODS: The 
      expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the 
      Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, 
      THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment 
      analysis, functional correlation analysis, immune filtration, Transcription 
      factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction 
      were performed following the identification of hub genes. RNA sequencing, in vivo 
      and in vitro experiments on rats were further performed to validate the 
      expression and function of the target gene. RESULTS: Five hub genes (ANGPTL4, 
      CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the 
      regulation of the immune system, extracellular matrix (ECM), and SMAD protein 
      signal transduction. There was a strong correlation between hub genes and 
      different functions, including lipid metabolism, mitochondrial function, and ECM 
      degradation. The immune filtration pattern grouped by disease and the expression 
      of hub genes showed significant changes in the immune cell composition. 
      TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin 
      showed great drug-targeting relevance based on potential drugs prediction of hub 
      genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase 
      activity, was eventually determined after hub gene screening, validation by 
      different datasets, RNA sequencing, and experiments. DISCUSSION: This study 
      screened five hub genes and ANGPTL4 was eventually determined as a potential 
      target for the regulation of the crosstalk in patients with IVDD and T2DM.
CI  - (c) 2023 Chen et al.
FAU - Chen, Yan
AU  - Chen Y
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, 200011, People's Republic of China.
FAU - Du, Han
AU  - Du H
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, 200011, People's Republic of China.
FAU - Wang, Xin
AU  - Wang X
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, 200011, People's Republic of China.
FAU - Li, Baixing
AU  - Li B
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, 200011, People's Republic of China.
FAU - Chen, Xuzhuo
AU  - Chen X
AD  - Department of Oral Surgery, Shanghai Key Laboratory of Stomatology & Shanghai 
      Research Institute of Stomatology, National Clinical Research Center for Oral 
      Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao 
      Tong University School of Medicine, Shanghai, 200011, People's Republic of China.
FAU - Yang, Xiao
AU  - Yang X
AUID- ORCID: 0000-0001-5653-3234
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, 200011, People's Republic of China.
FAU - Zhao, Changqing
AU  - Zhao C
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, 200011, People's Republic of China.
FAU - Zhao, Jie
AU  - Zhao J
AUID- ORCID: 0000-0003-1000-5641
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School 
      of Medicine, Shanghai, 200011, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20231227
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC10757813
OTO - NOTNLM
OT  - ANGPTL4
OT  - biomarker
OT  - functional analysis
OT  - intervertebral disc degeneration
OT  - type 2 diabetes mellitus
COIS- No conflict of interest exists declared by authors.
EDAT- 2024/01/02 11:45
MHDA- 2024/01/02 11:46
PMCR- 2023/12/27
CRDT- 2024/01/01 04:04
PHST- 2023/07/17 00:00 [received]
PHST- 2023/12/19 00:00 [accepted]
PHST- 2024/01/02 11:46 [medline]
PHST- 2024/01/02 11:45 [pubmed]
PHST- 2024/01/01 04:04 [entrez]
PHST- 2023/12/27 00:00 [pmc-release]
AID - 426439 [pii]
AID - 10.2147/JIR.S426439 [doi]
PST - epublish
SO  - J Inflamm Res. 2023 Dec 27;16:6361-6384. doi: 10.2147/JIR.S426439. eCollection 
      2023.