Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Prevention of lumbar disc degeneration through co-manipulation of insulin-like growth factor 1 and vascular endothelial growth factor

ABSTRACT:

Background

Associated with abnormal angiogenesis and disc dysfunction, lumbar disc degeneration (LDD) appears to be an important disease suffered by elderly people. Previous studies have highlighted the importance of insufficient insulin-like growth factor 1 (IGF1) and excessive vascular endothelial growth factor (VEGF) in the development and progression of LDD, though a practical therapeutic strategy is lacking.

Methods

The expression of IGF1 and VEGF was assessed in LDD specimens compared to normal disc tissue as a control. A gene therapy approach was performed, in which an adeno-associated virus (AAV) carrying both IGF1 and shVEGF (AAV-IGF1/shVEGF) was orthotopically injected to the rats that had undergone LDD. The alterations in IGF1 and VEGF levels in the treated disc tissue were confirmed by immunohistochemistry. The outcome of this therapy was assessed by disc cell death using an annexin V-FITC assay and by assessing lumbar proteoglycan and collagen II levels using ELISA.

Results

IGF1 expression was significantly downregulated in LDD, while VEGF expression was significantly upregulated in LDD, compared to normal controls. Combined AAV-IGF1/shVEGF treatment simultaneously corrected the insufficient IGF1 and the excessive VEGF in LDD rats. Moreover, AAV-IGF1/shVEGF significantly reduced disc cell death in the vertebral pulp and annulus fibrosus and significantly enhanced the lumbar proteoglycan and collagen II levels.

Conclusions

The simultaneous increase in IGF1 and depletion of VEGF effectively prevented the development of LDD, suggesting its potential as a novel therapeutic approach for LDD which is clinically translatable.

SUBMITTER: Ye Z

PROVIDER: S-EPMC8576649 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Vascular endothelial growth factor gene variations as a risk predictor in disc degeneration.

Project description:To evaluate the frequency of polymorphisms in the vascular endothelial growth factor (VEGF) gene, as well as to identify a potential risk haplotype among the polymorphic regions in this gene in patients with disc degeneration and in the Control Group.This study analyzed a total of 217 individuals distributed into the Disc Degeneration and Control Groups. Peripheral blood was collected from all patients to detect VEGF gene polymorphisms identified by qPCR (rs699947, rs1570360, rs2010963, rs833061 and rs3025039). All patients presenting disc degeneration had the confirmation by nuclear magnetic resonance test and were rated according to disc degeneration level.All polymorphisms were in Hardy- Weinberg equilibrium (p>0.05) in the studied population. The genotypic frequency for Disc Degeneration and Control Group were rs699947 p = 0.475, rs1570360 p = 0.862, rs2010963 p = 0.823, rs833061 p=0.596 and rs3025039 p=0.230. In haplotype analysis, the compositions CAGGC (p=0.094) and CCGGC (p=0.054) stood out.The correlation between VEGF gene polymorphism as a risk predictor for disc degeneration was negative in the studied population. However, the VEGF gene has a large polymorphic region, and it is activated by various catabolic and metabolic factors in the disc degeneration process, which has not been fully elucidated.

| S-EPMC5875151 | biostudies-literature

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

Project description: Not available

| S-EPMC6419319 | biostudies-literature

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

Project description: Not available

| S-EPMC4270425 | biostudies-literature

Targeting the insulin growth factor and the vascular endothelial growth factor pathways in ovarian cancer.

Project description:Antiangiogenic therapy is emerging as a highly promising strategy for the treatment of ovarian cancer, but the clinical benefits are usually transitory. The purpose of this study was to identify and target alternative angiogenic pathways that are upregulated in ovarian xenografts during treatment with bevacizumab. For this, angiogenesis-focused gene expression arrays were used to measure gene expression levels in SKOV3 and A2780 serous ovarian xenografts treated with bevacizumab or control. Reverse transcription-PCR was used for results validation. The insulin growth factor 1 (IGF-1) was found upregulated in tumor and stromal cells in the two ovarian xenograft models treated with bevacizumab. Cixutumumab was used to block IGF-1 signaling in vivo. Dual anti-VEGF and IGF blockade with bevacizumab and cixutumumab resulted in increased inhibition of tumor growth. Immunohistochemistry measured multivessel density, Akt activation, and cell proliferation, whereas terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay measured apoptosis in ovarian cancer xenografts. Bevacizumab and cixutumumab combination increased tumor cell apoptosis in vivo compared with therapy targeting either individual pathway. The combination blocked angiogenesis and cell proliferation but not more significantly than each antibody alone. In summary, IGF-1 activation represents an important mechanism of adaptive escape during anti-VEGF therapy in ovarian cancer. This study provides the rationale for designing bevacizumab-based combination regimens to enhance antitumor activity.

| S-EPMC4497519 | biostudies-literature

Omega-3 supplementation combined with anti-vascular endothelial growth factor lowers vitreal levels of vascular endothelial growth factor in wet age-related macular degeneration.

Project description:PurposeTo determine the influence of omega-3 supplementation on vitreous vascular endothelial growth factor A (VEGF-A) levels in patients with exudative age-related macular degeneration (wet AMD) receiving intravitreal anti-VEGF treatment.DesignProspective, randomized, open-label, single-center, clinical trial, consecutive interventional case series.MethodsThe study included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole. Twenty wet AMD patients being treated with anti-VEGF were randomized to daily supplementation of antioxidants, zinc, and carotenoids with omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid; group 1, n = 10) or without omega-3 fatty acids (group 2, n = 10). They were compared with an anti-VEGF treatment-naïve wet AMD group (group 3, n = 10) and an epiretinal membrane or macular hole group (group 4, n = 10). Primary outcome was vitreal VEGF-A levels (at the time of anti-VEGF injection). Secondary outcomes were plasma VEGF-A and central foveal thickness. Patients with new submacular hemorrhage or any other treatment within 3 months were excluded. Final analyses included 9, 6, 7, and 8 patients in groups 1 through 4, respectively.ResultsPatients receiving omega-3s (group 1) had significantly lower levels of vitreal VEGF-A (141.11 ± 61.89 pg/mL) when compared with group 2 (626.09 ± 279.27 pg/mL; P = .036) and group 3 (735.48 ± 216.43 pg/mL; P = .013), but similar levels to group 4 (235.81 ± 33.99 pg/mL; P = .215). All groups showed similar values for plasma VEGF-A and central foveal thickness measurements.ConclusionsThis study demonstrated that omega-3 supplementation combined with anti-VEGF treatment is associated with decreased vitreal VEGF-A levels in wet AMD patients.

| S-EPMC4389631 | biostudies-literature

Effects of suppressing bioavailability of insulin-like growth factor on age-associated intervertebral disc degeneration.

Project description:Suppression of the insulin-like growth factor-1 (IGF-1) signaling pathway reduces age-related disorders and increases lifespan across species, making the IGF-1 pathway a key regulator of aging. Previous in vitro intervertebral disc cell studies have reported the pro-anabolic effect of exogenously adding IGF-1 on matrix production. However, the overall effects of suppressing IGF-1 signaling on age-related intervertebral disc degeneration (IDD) is not known. Here, the effects of suppressing IGF-1 signaling on age-related IDD in vivo were examined using PAPPA -/- mice. These are animals with targeted deletion of pregnancy-associated plasma protein A (PAPPA), the major protease that cleaves inhibitory IGF binding proteins that control bioavailability of IGF-1 for cell signaling. Compared to age-matched wild-type (Wt) littermates, reduced levels of matrix proteoglycan (PG) and aggrecan were seen in discs of 23-month old PAPPA -/- mice. Decreased aggrecanolysis and expression of two key catabolic markers, matrix metalloproteinase-3 and a disintegrin and metalloproteinase with thrombospondin motifs-4, were also observed in discs of old PAPPA -/- mice compared to Wt littermates. Suppressing IGF-1 signaling has been implicated to shift cellular metabolism toward maintenance rather than growth and decreasing cellular senescence. Along this line, discs of old PAPPA -/- mice also exhibited lower cellular senescence, assessed by p53 and lamin B1 markers. Collectively, the data reveal complex regulation of disc matrix homeostasis by PAPPA/IGF-1 signaling during chronologic aging, that is, reduced IGF-1 bioavailability confers the benefit of decreasing disc cellular senescence and matrix catabolism but also the disadvantage of decreasing disc PG matrix anabolism. This pathway requires further mechanistic elucidation before IGF-1 could be considered as a therapeutic growth factor for treating IDD.

| S-EPMC7770198 | biostudies-literature

PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study

Project description:This is a phase 3, randomized, double-blind, placebo-controlled multi-center study evaluating the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia (FN) in patients with newly diagnosed, locally-advanced or metastatic colorectal cancer receiving first-line treatment with bevacizumab and either 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX) or 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI). This study will also investigate the effect of adding pegfilgrastim to bevacizumab and either FOLFOX or FOLFIRI by evaluating overall survival, progression-free survival, and overall response rate in each arm at regular intervals over a maximum of 60 months follow-up.

| 2073020 | ecrin-mdr-crc

Vascular endothelial growth factor pathway.

Project description: Not available

| S-EPMC3086058 | biostudies-literature

Full-Endoscopic Lumbar Interbody Fusion for Treating Lumbar Disc Degeneration Involving Disc Height Loss: Technical Report.

Project description:Background and Objectives: Lumbar disc degeneration (LDD) is the main cause of lower back pain and leads to corresponding disc height loss. Although lumbar interbody fusion (LIF) is commonly used for treating LDD, several different treatment strategies are available. We performed a minimally invasive full-endoscopic LIF (FELIF) using a uniportal full-endoscopic system. Materials and Methods: FELIF was performed for 12 patients with LDD with disc-height loss using a 4.1 mm working channel endoscope and a newly developed slider for cage insertion. The mean age of the patients was 68.3 years; the patients presented with single vertebral level involvement. The Brandner's disc index was used for evaluating the postoperative increase in the disc height. Preoperative and postoperative leg pain was evaluated using the numerical rating scale (NRS) score. Results: The mean operation time for FELIF was 109.4 min. The mean duration of hospital stay after FELIF was 7.7 days. There were no operative and postoperative complications, even without drainage during the mean follow-up period of 6.2 months (range, 2-10 months). The Brandner's disc index improved statistically significant (p > 0.01). The mean preoperative and postoperative NRS scores were 6.5 and 1.2, respectively. Conclusions: FELIF using a 4.1 mm working channel endoscope can be used for treating LDD with disc height loss. Radiculopathy caused by foraminal stenosis was the most suitable operative indication for FELIF.

| S-EPMC7559920 | biostudies-literature

Landscape of RNAs in human lumbar disc degeneration.

Project description:Accumulating evidence indicates noncoding RNAs (ncRNAs) fine-tune gene expression with mysterious machinery. We conducted a combination of mRNA, miRNA, circRNA, LncRNA microarray analyses on 10 adults' lumbar discs. Moreover, we performed additional global exploration on RNA interacting machinery in terms of in silico computational pipeline. Here we show the landscape of RNAs in human lumbar discs. In general, the RNA-abundant landscape comprises 14,635 mRNAs (37.93%), 2,059 miRNAs (5.34%), 18,995 LncRNAs (49.23%) and 2,894 (7.5%) circRNAs. Chromosome 1 contributes for RNA transcription at most (10%). Bi-directional transcription contributes evenly for RNA biogenesis, in terms of 5' to 3' and 3' to 5'. Despite the majority of circRNAs are exonic, antisense (1.49%), intergenic (0.035%), intragenic (1.69%), and intronic (6.29%) circRNAs should not be ignored. A single miRNA could interact with a multitude of circRNAs. Notably, CDR1as or ciRS-7 harbors 66 consecutive binding sites for miR-7-5p (previous miR-7), evidencing our pipeline. The majority of binding sites are perfect-matched (78.95%). Collectively, global landscape of RNAs sheds novel insights on RNA interacting mechanisms in human intervertebral disc degeneration.

| S-EPMC5325354 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data