Dataset Information

Elevated VEGF levels contribute to the pathogenesis of osteoarthritis.

ABSTRACT:

Background

The aim of our meta-analysis is to understand the relationship between the pathogenesis of osteoarthritis and the expression levels of vascular endothelial growth factor (VEGF) in multiple disease tissues in osteoarthritis patients.

Methods

The following electronic databases were searched, without language restrictions, to retrieve published studies relevant to VEGF and osteoarthritis: MEDLINE (1966?~?2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980?~?2013), CINAHL (1982?~?2013), Web of Science (1945?~?2013) and the Chinese Biomedical Database (CBM) (1982?~?2013). Meta-analysis of the extracted data was performed using the STATA statistical software. Standardized mean difference (SMD) with its corresponding 95% confidence interval (95% CI) was calculated.

Results

A total of 11 case-control studies, containing 302 osteoarthritis patients and 195 healthy controls, met our selection criteria for this meta-analysis. Our analyses of the data available from multiple disease tissues demonstrate that VEGF expression levels in osteoarthritis patients are significantly higher than healthy controls (SMD?=?1.18, 95% CI: 4.91?~?9.11, P??0.05).

Conclusion

Our meta-analysis provides evidence that higher VEGF expression levels strongly correlate with the pathogenesis of osteoarthritis.

SUBMITTER: Yuan Q

PROVIDER: S-EPMC4391471 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

Elevated VEGF levels contribute to the pathogenesis of osteoarthritis.

Yuan Quan Q Sun Li L Li Jian-Jun JJ An Chun-Hou CH

BMC musculoskeletal disorders 20141217

<h4>Background</h4>The aim of our meta-analysis is to understand the relationship between the pathogenesis of osteoarthritis and the expression levels of vascular endothelial growth factor (VEGF) in multiple disease tissues in osteoarthritis patients.<h4>Methods</h4>The following electronic databases were searched, without language restrictions, to retrieve published studies relevant to VEGF and osteoarthritis: MEDLINE (1966 ~ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ~ ...[more]

PMID: 25515407

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Project description:BackgroundGrb2-associated binder 2 (Gab2) is a scaffolding protein that serves as a critical signaling amplifier downstream of tyrosine kinase receptors. Our previous study has shown that Gab2 induces epithelial-to-mesenchymal transition (EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of Gab2 in CRC growth and angiogenesis remains unclear.MethodsThe expression of vascular endothelial growth factor (VEGF) in different colorectal tissues was detected by immunohistochemistry and qRT-PCR to evaluate its correlation with Gab2. Lentiviral vectors bearing Gab2 gene and its small interfering RNAs were constructed and transfected into CRC cell lines. The effects of Gab2 on the cell proliferation in vitro and tumorigenesis in vivo, were examined via CCK‑8 assay, colony formation assay as well as tumorigenicity assay respectively. Moreover, to assess its potential role in tumor growth and angiogenesis, the expression of Ki67, CD34 and vascular endothelial growth factor receptor-2 (VEGFR2) were detected by immunohistochemistry in CRC cells tumors. Finally, we evaluated the impact of Gab2 on the expression of c-Myc and VEGF, and the probable effect of mechanistic targeted extracellular signal-regulated kinase (ERK) pathway in suppressing tumor growth and angiogenesis.ResultsUp-regulation of Gab2 expression was found to be positively correlated with VEGF in CRC tissues. Exogenous expression of Gab2 obviously promoted, whereas silencing of Gab2 inhibited, proliferation and clone formation of human CRC cells in vitro. Of note, Gab2 enhanced tumorigenesis and tumor growth in mouse xenografts with high Ki67 expression, and led to an increased vessel density with strong CD34 and VEGFR2 activity. In addition, elevated Gab2 expression obviously up-regulated the expression of VEGF, and stimulated the activation of its downstream genes, ERK1/2 and c-Myc in CRC cells. Instead, down-regulated Gab2 expression significantly reduced the levels of VEGF, and inhibited the transduction of ERK/c-Myc pathway. Finally, we revealed that mechanistic target of mitogen-activated protein kinase (MEK) could attenuate Gab2-induced tumor growth and angiogenesis via altering VEGF and c-Myc levels.ConclusionsThe results from our study suggest that Gab2 promotes intestinal tumor growth and angiogenesis through upregulation of VEGF expression mediated by the MEK/ERK/c-Myc pathway.

Project description:IntroductionThe identification of reliable prognostic factors is a crucial requirement for patients with IgA nephropathy (IgAN). Here, we explored the relationship between serum chloride levels and prognosis in patients with IgAN.MethodsWe recruited all patients with primary IgAN, as diagnosed by renal biopsy, between 1st January 2015 and 1st April 2019. Patients were divided two groups (high chloride group and low chloride group) based on the best cut-off values from survival receiver operating characteristic (ROC) curves. The baseline clinicopathological characteristics of two groups were then compared. Cox proportional hazard models were used to determine the prognostic value of serum chloride levels in patients with IgAN. Finally, we screened reliable prognostic indicators and built a clinical prediction model and validated the performance of the model.ResultsCompared with patients in the high chloride group, patients in the low chloride group had significantly lower levels of 24-hour urinary total protein (24 h-UTP), serum creatinine (sCr), and higher levels of hemoglobin (Hb), albumin (all p < 0.05), and less proportion of Oxford classification grade E1 (endothelial cell proliferation) and T2 (renal tubule atrophy or renal interstitial fibrosis). Cox analysis revealed that serum chloride level ≥ 105.4 mmol/L was a significant and independent risk factor for prognosis in patients with IgAN (p < 0.05). Serum chloride, sCr, T, hypertension, and Hb were used to generate a predictive model for prognosis. Thec-indices of our predictive model were 0.80, 0.86, and 0.78, for 1, 2, and 3 years, respectively; Brier scores were 0.06, 0.09, and 0.16, respectively.ConclusionsA serum chloride level ≥ 105.4 mmol/l was identified as a significant and independent risk factor for the prognosis of patients with IgAN. A predictive prognosis model was generated using serum chloride, sCr, T, hypertension, and Hb; this model exhibited a good predictive effect.

Dataset Information

Elevated VEGF levels contribute to the pathogenesis of osteoarthritis.

Background

Methods

Results

Conclusion

Publications

Elevated VEGF levels contribute to the pathogenesis of osteoarthritis.

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