HGF induces oncoprotein HCCR-1 expression through the Wnt/β-catenin pathway in gastric cancer.

Objective: Human cervical cancer oncogene (HCCR)-1, previously identified in cervical cancer and its cell lines, has been reported to play an important role in tumor progression in several cancers as a suppressor of apoptosis. However, the role of in the tumorigenesis of stomach cancer has not been identified. This study examined the role of as a suppressor of apoptosis during tumorigenesis in gastric cancer, along with its possible regulatory pathway.

Inhibitory effects of quercetagetin 3,4'-dimethyl ether purified from Inula japonica on cellular senescence in human umbilical vein endothelial cells.

Cellular senescence contributes to tissue and organismal aging, tumor suppression and progress, tissue repair and regeneration, and age-related diseases. Thus, aging intervention might be beneficial for treatment and prevention of diverse age-related diseases. In the present study, we investigated whether four compounds purified from Inula japonica exert inhibitory activity against cellular senescence induced by adriamycin in human umbilical vein endothelial cells (HUVECs).

Chemical constituents of Hericium erinaceum associated with the inhibitory activity against cellular senescence in human umbilical vascular endothelial cells.

Hericium erinaceum is an edible and medicinal mushroom widely used in Korea, Japan, and China. On the search for biologically active compounds supporting the medicinal usage, the MeOH extract of the fruiting bodies of H. erinaceum was investigated for its chemical constituents.

RGS2 suppresses breast cancer cell growth via a MCPIP1-dependent pathway.

Regulator of G protein signaling 2 (RGS2) is a member of a family of proteins that functions as a GTPase-activating protein (GAP) for Gα subunits. RGS2 mRNA expression is lower in breast cancerous tissues than in normal tissues. In addition, expression of RGS2 is also lower in MCF7 (cancerous breast cells) than in MCF10A (normal breast cells).

Microtubule stabilization attenuates vascular calcification through the inhibition of osteogenic signaling and matrix vesicle release.

Vascular calcification is a strong predictor of cardiovascular morbidity and mortality, especially in individuals with chronic kidney disease or diabetes. The mechanism of vascular calcification has remained unclear, however, and no effective therapy is currently available. Our study was aimed at identifying the role of dynamic remodeling of microtubule cytoskeletons in hyperphosphatemia-induced vascular calcification.

Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in male mice.

The present study examined the role of clusterin in insulin resistance in high fat-fed wild-type and clusterin knockout (KO) mice. The plasma levels of glucose and C-peptide and islet size were increased in clusterin KO mice after an 8-week high-fat diet. In an ip glucose tolerance test, the area under the curve for glucose was not different, whereas the area under the curve for insulin was higher in clusterin KO mice.

Relation of atrial fibrillation (AF) and change of lipoproteins: male patients with AF exhibited severe pro-inflammatory and pro-atherogenic properties in lipoproteins.

Objectives: This study was designed to search putative biomarkers for detection of relatively young-onset atrial fibrillation (AF).

Design And Methods: We analyzed serum lipoproteins from male patients with paroxysmal AF (48±9years old, n=29) and controls with similar age (50±10years old, n=27), who visited our hospital for radiofrequency catheter ablation due to paroxysmal supraventricular tachycardia.

Results: Although the AF group showed normal serum cholesterol level, they exhibited 16% lower HDL-cholesterol and 13% higher serum cholesteryl ester transfer protein activity than those of the control group.

High glucose induces connective tissue growth factor expression and extracellular matrix accumulation in rat aorta vascular smooth muscle cells via extracellular signal-regulated kinase 1/2.

Connective tissue growth factor (CTGF) is a potent pro-fibrotic factor, which is implicated in fibrosis through extracellular matrix (ECM) induction in diabetic cardiovascular complications. It is an important downstream mediator in the fibrotic action of transforming growth factor β (TGFβ) and is potentially induced by hyperglycemia in human vascular smooth muscle cells (VSMCs). Therefore, the goal of this study is to identify the signaling pathways of CTGF effects on ECM accumulation and cell proliferation in VSMCs under hyperglycemia.

Acetylcholine-induced AMP-activated protein kinase activation attenuates vasoconstriction through an LKB1-dependent mechanism in rat aorta.

Numerous studies of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries have been reported since the original description by Furchgott and Zawadzki (1980). ACh also produces endothelium-independent relaxation. However, it is still unknown whether ACh-induced AMP-activated protein kinase (AMPK) activation can attenuate vasoconstriction in endothelium-denuded rat aorta.

Insulin Like Growth Factor Binding Protein-5 Regulates Excessive Vascular Smooth Muscle Cell Proliferation in Spontaneously Hypertensive Rats via ERK 1/2 Phosphorylation.

Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY).

HJURP regulates cellular senescence in human fibroblasts and endothelial cells via a p53-dependent pathway.

Holliday junction recognition protein (HJURP), a centromere protein-A (CENP-A) histone chaperone, mediates centromere-specific assembly of CENP-A nucleosome, contributing to high-fidelity chromosome segregation during cell division. However, the role of HJURP in cellular senescence of human primary cells remains unclear. We found that the expression levels of HJURP decreased in human dermal fibroblasts and umbilical vein endothelial cells in replicative or premature senescence.

TLR2 stimulates ABCA1 expression via PKC-η and PLD2 pathway.

ATP-binding cassette transporter A1 (ABCA1) is a membrane-bound protein that regulates cardiovascular disease including atherosclerosis by the efflux of excess cholesterol from cells and by suppression of inflammation. Using a mouse macrophage cell line Raw264.7, we studied the importance of toll-like receptor 2 (TLR2) on ABCA1 expression and the signaling pathway responsible for TLR2-mediated ABCA1 expression.

Role of JAK2-STAT3 in TLR2-mediated tissue factor expression.

Tissue factor (TF) is a core protein with an essential function in the coagulation cascade that maintains the homeostasis of the blood vessels. TF not only participates in neointima formation, but also causes the development of atherosclerosis. This study investigated the mechanism regulating TF expression in macrophages using Pam3 CSK4 , a TLR2 ligand.

Mitotic centromere-associated kinase (MCAK/Kif2C) regulates cellular senescence in human primary cells through a p53-dependent pathway.

Mitotic centromere-associated kinase (MCAK/Kif2C) plays a critical role in chromosome movement and segregation with ATP-dependent microtubule depolymerase activity. However, its role in cellular senescence remains unclear. MCAK/Kif2C expression decreased in human primary cells under replicative and premature senescence.

Metformin inhibits inflammatory response via AMPK-PTEN pathway in vascular smooth muscle cells.

Atherosclerosis is a chronic inflammation of the coronary arteries. Vascular smooth muscle cells (VSMCs) stimulated by cytokines and chemokines accelerate the inflammatory response and migrate to the injured endothelium during the progression of atherosclerosis. Activation of AMP activated protein kinase (AMPK), a key sensor maintaining metabolic homeostasis, suppresses the inflammatory response.

Resveratrol inhibits inflammation induced by heat-killed Listeria monocytogenes.

Resveratrol is a polyphenolic compound in red wine that has antioxidant and cardioprotective effects in animal models. Listeria monocytogenes is a pathogen that mainly affects immunocompromised individuals and is initially detected at the cell surface or in phagosomes by toll-like receptor 2. Many antioxidants also exert anti-inflammatory activities; therefore, we evaluated the anti-inflammatory properties of resveratrol by studying the various inflammatory responses induced by heat-killed L.

The role of nacreous factors in preventing osteoporotic bone loss through both osteoblast activation and osteoclast inactivation.

Excessive bone resorption by osteoclasts relative to bone formation by osteoblasts results in the development of osteoporosis. Anti-osteoporotic agents that are able both to inhibit bone resorption and to stimulate bone formation are not available. We now show that water-soluble nacreous factors prepared from the pearl oyster Pteria martensii prevent osteoporotic bone loss associated with estrogen deficiency in mice mainly through osteoclast inactivation.

A point mutant of apolipoprotein A-I (V156K) showed enhancement of cellular insulin secretion and potent activity of facultative regeneration in zebrafish.

Sensitivity of glycation and functional changes were compared between wild-type (WT) and the V156K mutant of apolipoprotein A-I in the reconstituted high-density lipoproteins (rHDL) state. WT-rHDL showed increased production of advanced glycated end (AGE) products with proteolytic fragmentation by fructose treatment (final 5 mM) for 48 hr; however, V156K-rHDL was more resistant to the same fructosylation and protein cleavage. Glycated WT-rHDL severely lost antioxidant activity; in contrast, V156K-rHDL showed much less AGE production and retained stronger antioxidant properties in the glycated state.

Metformin-induced AMP-activated protein kinase activation regulates phenylephrine-mediated contraction of rat aorta.

The aim of the present study is to determine the effects and molecular mechanisms by which activation of LKB1-AMP-activated protein kinase (AMPK) by metformin regulates vascular smooth muscle contraction. The essential ability of vascular smooth muscle cells (VSMCs) to contract and relax in response to an elevation and reduction in intravascular pressure is necessary for appropriate blood flow regulation. Thus, vessel contraction is a critical mechanism for systemic blood flow regulation.

Extracellular acidosis accelerates bone resorption by enhancing osteoclast survival, adhesion, and migration.

Acidic extracellular pH promotes osteoporotic bone loss by osteoclast activation. However, the change of osteoclastic cell behavior in acidosis-stimulated bone resorption process is unknown. We found that lowering extracellular pH induced an increase in the survival, adhesion, and migration of mature osteoclasts with a full actin ring, leading to enhanced pit formation on dentine slices.

The JAK2-Akt-glycogen synthase kinase-3β signaling pathway is involved in toll-like receptor 2-induced monocyte chemoattractant protein-1 regulation.

Monocyte chemoattractant protein-1 (MCP-1) is an essential cytokine for the migration of monocytes into vessels, and is also involved in the pathogenesis of atherosclerosis. In this study, we investigated the importance of janus kinase 2 (JAK2) and the function of the Akt and glycogen synthase kinase-3β (GSK3β) pathway in toll-like receptor (TLR2)-mediated MCP-1 expression. The TLR2 agonist, Pam3CSK4, induced MCP-1 expression in the Raw264.

TRAIL is involved in CpG ODN-mediated anti-apoptotic signals.

Synthetic oligodeoxynucleotides (ODNs) with the CpG-motifs are recognized by toll-like receptor 9 (TLR9), which elicits an immune response. Serum starvation of Raw264.7 cells increased tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression.

RGS2 is a negative regulator of STAT3-mediated Nox1 expression.

NADPH oxidase 1 (Nox1) is essential for reactive oxygen species production in the innate immune responses mediated by toll-like receptor (TLR), but the mechanism regulating its expression remains uncertain. Here, we find that Nox1 induction is TLR2-dependent, but independent of myeloid differentiation primary response gene 88 (MyD88). We demonstrate the capacity of signal transducer and activator of transcription 3 (STAT3) to activate Nox1's transcription, as well as cooperative regulation by janus kinase 1 and 3 (JAK1 and JAK3).

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway.

Vascular cell senescence, induced by the DNA damage response or inflammatory stress, contributes to age-associated vascular disease. Using complementary DNA microarray technology, we found that the level of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is downregulated during endothelial cell (EC) senescence. PATZ1 may have an important role as a transcriptional repressor in chromatin remodeling and transcription regulation; however, the role of PATZ1 in EC senescence and vascular aging remains unidentified.