DICAM inhibits angiogenesis via suppression of AKT and p38 MAP kinase signalling

Han, Seung-Woo; Jung, Youn‐Kwan; Lee, Eun‐Ju; Park, Hyeri; Kim, Gun-Woo; Jeong, Jong Hwa; Han, Min-Su; Choi, Je‐Yong

doi:10.1093/cvr/cvt019

Cited by 34 publications

(30 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our gene array data show an overall up-regulation of proangiogenic genes involved in different steps of neoangiogenesis, such as GPC4, abundantly expressed in PsA synovium [75], and MAPK11, also known as p38β, a downstream target of VEGF signaling during angiogenesis [78]. An increased expression for MUC1, an activator of multiple pro-angiogenic factors during hypoxia-driven angiogenesis [134], typical of inflammatory joint diseases [135], was also observed.…”

Section: Discussionmentioning

confidence: 89%

See 1 more Smart Citation

Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis

et al. 2015

View full text Add to dashboard Cite

BackgroundPsoriatic arthritis (PsA) is an inflammatory arthritis whose pathogenesis is poorly understood; it is characterized by bone erosions and new bone formation. The diagnosis of PsA is mainly clinical and diagnostic biomarkers are not yet available. The aim of this work was to clarify some aspects of the disease pathogenesis and to identify specific gene signatures in paired peripheral blood cells (PBC) and synovial biopsies of patients with PsA. Moreover, we tried to identify biomarkers that can be used in clinical practice.MethodsPBC and synovial biopsies of 10 patients with PsA were used to study gene expression using Affymetrix arrays. The expression values were validated by Q-PCR, FACS analysis and by the detection of soluble mediators.ResultsSynovial biopsies of patients showed a modulation of approximately 200 genes when compared to the biopsies of healthy donors. Among the differentially expressed genes we observed the upregulation of Th17 related genes and of type I interferon (IFN) inducible genes. FACS analysis confirmed the Th17 polarization. Moreover, the synovial trascriptome shows gene clusters (bone remodeling, angiogenesis and inflammation) involved in the pathogenesis of PsA. Interestingly 90 genes are modulated in both compartments (PBC and synovium) suggesting that signature pathways in PBC mirror those of the inflamed synovium. Finally the osteoactivin gene was upregulared in both PBC and synovial biopsies and this finding was confirmed by the detection of high levels of osteoactivin in PsA sera but not in other inflammatory arthritides.ConclusionsWe describe the first analysis of the trancriptome in paired synovial tissue and PBC of patients with PsA. This study strengthens the hypothesis that PsA is of autoimmune origin since the coactivity of IFN and Th17 pathways is typical of autoimmunity. Finally these findings have allowed the identification of a possible disease biomarker, osteoactivin, easily detectable in PsA serum.

show abstract

Section: Discussionmentioning

confidence: 89%

“…Differentially expressed genes also comprise transcripts which regulate the angiogenesis process [75–78]. …”

Section: Resultsmentioning

confidence: 99%

Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Previous studies have defined AKT-mediated signaling pathways that promoted increased cell viability [58] and were initiated by VEGFR2 phosphorylation and binding of α V β 3 integrin to cell adhesion ligands [59]. VEGFR2 and α V β 3 integrins are also known to behave synergistically, as binding of α V β 3 integrins to adhesion ligands enhances VEGFR2 activity and vice-versa [16].…”

Section: Discussionmentioning

confidence: 99%

Differential effects of cell adhesion, modulus and VEGFR-2 inhibition on capillary network formation in synthetic hydrogel arrays

et al. 2014

View full text Add to dashboard Cite

Efficient biomaterial screening platforms can test a wide range of extracellular environments that modulate vascular growth. Here, we used synthetic hydrogel arrays to probe the combined effects of Cys-Arg-Gly-Asp-Ser (CRGDS) cell adhesion peptide concentration, shear modulus and vascular endothelial growth factor receptor 2 (VEGFR2) inhibition on human umbilical vein endothelial cell (HUVEC) viability, proliferation and tubulogenesis. HUVECs were encapsulated in degradable poly(ethylene glycol) (PEG) hydrogels with defined CRGDS concentration and shear modulus. VEGFR2 activity was modulated using the VEGFR2 inhibitor SU5416. We demonstrate that synergy exists between VEGFR2 activity and CRGDS ligand presentation in the context of maintaining HUVEC viability. However, excessive CRGDS disrupts this synergy. HUVEC proliferation significantly decreased with VEGFR2 inhibition and increased modulus, but did not vary monotonically with CRGDS concentration. Capillary-like structure (CLS) formation was highly modulated by CRGDS concentration and modulus, but was largely unaffected by VEGFR2 inhibition. We conclude that the characteristics of the ECM surrounding encapsulated HUVECs significantly influence cell viability, proliferation and CLS formation. Additionally, the ECM modulates the effects of VEGFR2 signaling, ranging from changing the effectiveness of synergistic interactions between integrins and VEGFR2 to determining whether VEGFR2 upregulates, downregulates or has no effect on proliferation and CLS formation.

show abstract

“…Recombinant adenovirus (Ad) expressing full-length Dicam (Ad-Dicam) or control b-galactosidase (Ad-LacZ) was prepared for in vitro gain-of-function of Dicam as described previously 15 . Primary chondrocytes (5 Â 10 5 /well) were seeded in 6-well plates and infected with 100 multiplicity of infection (m.o.i.)…”

Section: Adenovirus and Adeno-associated Virus (Aav) Transductionmentioning

confidence: 99%

Dicam promotes proliferation and maturation of chondrocyte through Indian hedgehog signaling in primary cilia

Han

Park

Lee

et al. 2018

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

show abstract

DICAM inhibits angiogenesis via suppression of AKT and p38 MAP kinase signalling

Abstract: Collectively, DICAM suppressed angiogenesis by attenuating AKT and p38 MAP kinase signalling, which suggests that DICAM may be a novel negative regulator of angiogenesis.

Cited by 34 publications

References 35 publications

Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis

Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis

Differential effects of cell adhesion, modulus and VEGFR-2 inhibition on capillary network formation in synthetic hydrogel arrays

Dicam promotes proliferation and maturation of chondrocyte through Indian hedgehog signaling in primary cilia

Contact Info

Product

Resources

About