Quantitative Proteomics Reveals β2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability

Jo, Dong Hyun; Bae, Jingi; Chae, Sehyun; Kim, Jin Hyoung; Han, Jiyou; Hwang, Daehee; Lee, Sang Won; Kim, Jeong Hun

doi:10.1074/mcp.m115.053249

Cited by 15 publications

(8 citation statements)

References 46 publications

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“…For the aligned peptides, we identified 2461 unique peptides (DEpeptides) showing significant ( P < 0.05) upregulation or downregulation by oleate treatment using the integrative statistical method previously reported 35 (Methods and materials). We then identified 349 DSPs that have two or more DEpeptides showing consistent upregulation or downregulation by oleate treatment as previously described 46 (Methods and materials). We excluded 12 DSPs having both two or more upregulated and downregulated DEpeptides.…”

Section: Resultsmentioning

confidence: 99%

A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Park

Jung

et al. 2018

Exp Mol Med

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Increased fatty acid (FA) is often observed in highly proliferative tumors. FAs have been shown to modulate the secretion of proteins from tumor cells, contributing to tumor survival. However, the secreted factors affected by FA have not been systematically explored. Here, we found that treatment of oleate, a monounsaturated omega-9 FA, promoted the proliferation of HepG2 cells. To examine the secreted factors associated with oleate-induced cell proliferation, we performed a comprehensive secretome profiling of oleate-treated and untreated HepG2 cells. A comparison of the secretomes identified 349 differentially secreted proteins (DSPs; 145 upregulated and 192 downregulated) in oleate-treated samples, compared to untreated samples. The functional enrichment and network analyses of the DSPs revealed that the 145 upregulated secreted proteins by oleate treatment were mainly associated with cell proliferation-related processes, such as lipid metabolism, inflammatory response, and ER stress. Based on the network models of the DSPs, we selected six DSPs (MIF, THBS1, PDIA3, APOA1, FASN, and EEF2) that can represent such processes related to cell proliferation. Thus, our results provided a secretome profile indicative of an oleate-induced proliferation of HepG2 cells.

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Section: Resultsmentioning

confidence: 99%

A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Park

Jung

et al. 2018

Exp Mol Med

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“…In contrast to diminished NO availability, VEGF induces abnormal endothelial cell proliferation via VEGFR2 and, more importantly, enhances migration but disrupts cytoskeleton rearrangement through cross talk between VEGFR2 and integrin α 5 β 3 or integrin β 2, separately [ 52 , 53 ]. Moreover, under physical angiogenesis, Notch/VEGFR2 modulates differential dynamics of VE-cadherin junction pattern during sprouting.…”

Section: Abnormal Angiogenesis In Diabetic Retinopathy and Nephropmentioning

confidence: 99%

“…The pathological pattern “VEGF uncoupling with NO” is preserved and serves as the main mechanism in diabetic retinopathy and nephrology [ 52 , 57 ]. For instance, studies from diabetic eNOS knockout mice have demonstrated that this mouse model develops severe albuminuria as well as increased VEGF expression in the kidney.…”

Section: Abnormal Angiogenesis In Diabetic Retinopathy and Nephropmentioning

confidence: 99%

Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

Zhang

Yuan

et al. 2016

Stem Cells International

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Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

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“…Fresh frozen surgical tumor tissues were individually cryopulverized using a Cryoprep device (CP02, Covaris) as described previously [15]. Briefly, each tissue piece (30–130 mg in wet tissue weight) was placed in a cryovial (Covaris, 430487) on dry ice and then transferred to a Covaris tissue bag (TT5 extra thick, Covaris), which was immersed in liquid nitrogen for 30 s. The tissue was pulverized using different impact levels depending on the total weight of the tissue (< 50 mg: impact level 2; 50–150 mg: level 3).…”

Section: Methodsmentioning

confidence: 99%

“…The lysate was digested using the FASP protocol as described previously [15]. The proteins were reduced in SDT buffer (4% SDS in 0.1 M Tris-HCl, pH 7.6, and 0.1 M DTT) at 37 °C for 45 min with shaking at 300 rpm and boiled for 10 min at 95 °C on a thermomixer (Comfort, Eppendorf).…”

Section: Methodsmentioning

confidence: 99%

Comprehensive proteome and phosphoproteome profiling shows negligible influence of RNAlater on protein abundance and phosphorylation

et al. 2019

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Certain tumors such as pancreatic ductal adenocarcinoma (PDAC) are known to contain a variety of hydrolytic enzymes including RNases and proteases that may lead to degradation of RNA and proteins during sample processing. For such tumor tissues with RNA instability, RNAlater containing a high concentration of quaternary ammonium sulfates that denature RNA-hydrolyzing enzymes is often used to protect RNAs from hydrolysis. Although a few studies have been carried out to determine the effect of RNAlater on DNA and RNA, whether RNAlater influences the proteome and phosphoproteome is largely unknown. In this study we carried out a systematic and comprehensive analysis of the effect of RNAlater on the proteome and phosphoproteome using high-resolution mass spectrometry. PDAC tissues from three patients were individually pulverized and the tissue powders of each patient were divided into two portions, one of which was incubated in RNAlater at 4 °C for 24 h (RNAlater tissue) while the other was kept at – 80 °C (frozen tissue). Comprehensive quantitative profiling experiments on the RNAlater tissues and the frozen tissues resulted in the identification of 99,136 distinct peptides of 8803 protein groups and 17,345 phosphopeptides of 16,436 phosphosites. The data exhibited no significant quantitative changes in both proteins and phosphorylation between the RNAlater tissues and the frozen tissue. In addition, the phosphoproteome data showed heterogeneously activated pathways among the three patients that were not altered by RNAlater. These results indicate that the tissue preservation method using RNAlater can be effectively used on PDAC tissues for proteogenomic studies where preservation of intact DNA, RNA and proteins is prerequisite. Data from this study are available via ProteomeXchange with the identifier PXD010710. Electronic supplementary material The online version of this article (10.1186/s12014-019-9239-z) contains supplementary material, which is available to authorized users.

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Quantitative Proteomics Reveals β2 Integrin-mediated Cytoskeletal Rearrangement in Vascular Endothelial Growth Factor (VEGF)-induced Retinal Vascular Hyperpermeability

Cited by 15 publications

References 46 publications

A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

Comprehensive proteome and phosphoproteome profiling shows negligible influence of RNAlater on protein abundance and phosphorylation

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