High glucose mediates the ChREBP/p300 transcriptional complex to activate proapoptotic genes Puma and BAX and contributes to intervertebral disc degeneration

Feng, Yuping; Wang, Hantao; Chen, Zhi; Chen, Bin

doi:10.1016/j.bone.2021.116164

Cited by 12 publications

(6 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this only partially explains the genetic involvement and lacks thorough analysis. 57 , 58 Furthermore, diabetes-related products, such as amyloid protein, leptin, and glucagon-like peptide-1 (GLP-1, a safe polypeptide hormone for treating T2DM), are also related to IVDD. However, the exact molecular mechanisms underlying crosstalk between IVDD and T2DM remain unclear.…”

Section: Discussionmentioning

confidence: 99%

ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models

Chen,

Du,

Wang

et al. 2023

JIR

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models

Chen,

Du,

Wang

et al. 2023

JIR

View full text Add to dashboard Cite

show abstract

“…identified a significant increase in apoptosis ratio of NP cells under mechanical compression in a dose‐dependent manner, and further signaling pathway research indicated RSV treatment appeared to be effective in alleviating NP cells apoptosis via ERK1/2 pathway. Recent research has confirmed that diabetes is a potential causative factor of IDD 80,81 . Wang et al 82 .…”

Section: Molecular Actions Of Rsv In the Prevention Of Iddmentioning

confidence: 93%

“…Recent research has confirmed that diabetes is a potential causative factor of IDD. 80 , 81 Wang et al . 82 treated high glucose induced human NP cells with RSV and RSV + PI3K inhibitor LY294002, respectively.…”

Section: Molecular Actions Of Rsv In the Preventio...mentioning

confidence: 99%

Pharmacological Effects of Resveratrol in Intervertebral Disc Degeneration: A Literature Review

Liu

Zhang

Zang

et al. 2022

Orthopaedic Surgery

View full text Add to dashboard Cite

Intervertebral disc degeneration (IDD) is a high incidence disease of musculoskeletal system that often leads to stenosis, instability, pain and even deformity of the spinal segments. IDD is an important cause of discogenic lower back pain and often leads to large economic burden to families and society. Currently, the treatment of IDD is aimed at alleviating symptoms rather than blocking or reversing pathological progression of the damaged intervertebral disc. Resveratrol (RSV) is a polyphenol phytoalexin first extracted from the Veratrum grandiflflorum O. Loes and can be found in various plants and red wine. Owing to the in-depth study of pharmacological mechanisms, the therapeutic potential of RSV in various diseases such as osteoarthritis, neurodegenerative diseases, cardiovascular diseases and diabetes have attracted the attention of many researchers. RSV has anti-apoptotic, anti-senescent, anti-inflammatory, anti-oxidative, and anabolic activities, which can prevent further degeneration of intervertebral disc cells and enhance their regeneration. With high safety and various biological functions, RSV might be a promising candidate for the treatment of IDD. This review summarizes the biological functions of RSV in the treatment of IDD and to facilitate further research.

show abstract

“…Using isothermal titration calorimetry, Han et al [ 267 ] showed that PUMA binds to the DBD of p53 and thus induces apoptosis by a transcriptionally non-dependent mechanism. In IDD, basal p53 expression [ 37 ] and phosphorylated and acetylated p53 levels are significantly elevated in degenerative IVD cells [ 112 , 268 ], leading to PUMA and Bax accumulation and mitochondrial dysfunction, which in turn leads to apoptosis [ 104 , 269 ]. In addition, compression loading increases the expression of p53 in NPC mitochondria in a time-dependent manner, whereas the inhibition of p53 mitochondrial translocation by pifithrin (PFT) significantly reduces compression-induced NPC apoptosis, suggesting that p53 may promote apoptosis by interacting with Bcl-2 family proteins through mitochondrial translocation [ 109 ].…”

Section: The Role Of P53 In Iddmentioning

confidence: 99%

Emerging role and therapeutic implications of p53 in intervertebral disc degeneration

Wang,

Hu,

Zhang

et al. 2023

Cell Death Discov.

View full text Add to dashboard Cite

Lower back pain (LBP) is a common degenerative musculoskeletal disease that imposes a huge economic burden on both individuals and society. With the aggravation of social aging, the incidence of LBP has increased globally. Intervertebral disc degeneration (IDD) is the primary cause of LBP. Currently, IDD treatment strategies include physiotherapy, medication, and surgery; however, none can address the root cause by ending the degeneration of intervertebral discs (IVDs). However, in recent years, targeted therapy based on specific molecules has brought hope for treating IDD. The tumor suppressor gene p53 produces a transcription factor that regulates cell metabolism and survival. Recently, p53 was shown to play an important role in maintaining IVD microenvironment homeostasis by regulating IVD cell senescence, apoptosis, and metabolism by activating downstream target genes. This study reviews research progress regarding the potential role of p53 in IDD and discusses the challenges of targeting p53 in the treatment of IDD. This review will help to elucidate the pathogenesis of IDD and provide insights for the future development of precision treatments.

show abstract

High glucose mediates the ChREBP/p300 transcriptional complex to activate proapoptotic genes Puma and BAX and contributes to intervertebral disc degeneration

Cited by 12 publications

References 36 publications

ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models

ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models

Pharmacological Effects of Resveratrol in Intervertebral Disc Degeneration: A Literature Review

Emerging role and therapeutic implications of p53 in intervertebral disc degeneration

Contact Info

Product

Resources

About