Omer Faruk Hatipoglu

• PhD
• Professor (Assistant) at Turgut Özal University

Introduction Tumor necrosis factor-α (TNF-α)-induced angiogenesis plays a critical role in tumor progression and metastasis, making it an important therapeutic target in cancer treatment. Suppressing angiogenesis can effectively limit tumor growth and metastasis. However, despite advancements in understanding angiogenic pathways, effective strategi...

Chondrocytes are responsible for the production of extracellular matrix (ECM) components of cartilage, such as collagen type II alpha-1 (COL2A1) and aggrecan, which are loosely distributed in articular cartilage. Chondrocyte dysfunction has been implicated in the pathogenesis of rheumatic diseases, such as osteoarthritis (OA) and rheumatoid arthrit...

We previously found that ribosomal protein L9 (RPL9) is a novel advanced glycation end product (AGE)‐binding protein that can decrease pro‐inflammatory TNF‐α expression stimulated by lipopolysaccharide (LPS) plus high‐mobility group box 1 (HMGB1), suggesting that RPL9 has a role in regulating LPS+HMGB1‐stimulated inflammatory reactions. Among the v...

Advanced glycation end products (AGEs) are a heterogeneous group of compounds that are non-enzymatically produced by reactions between carbonyl compounds and proteins. Many types of AGEs are produced according to the type or concentration of the reacting carbonyl compound. We have previously demonstrated that a glycolaldehyde-derived AGE suppresses...

Background Advanced glycation end products (AGEs) are heterogeneous proinflammatory molecules produced by a non-enzymatic glycation reaction between reducing sugars (and their metabolites) and biomolecules with amino groups, such as proteins. Although increases in and the accumulation of AGEs have been implicated in the onset and exacerbation of li...

Histamine is a well-known inflammatory mediator, but how histamine induces angiogenesis remains poorly understood. In the present study, we demonstrated a dose-dependent dynamic tube formation in the human endothelial cell line EA.hy926 in the presence of histamine that was completely blocked by histamine H1 receptor (H1R) and protein kinase C (PKC...

Background: Advanced glycation end products (AGEs) are heterogeneous proinflammatory molecules produced by a non-enzymatic glycation reaction between reducing sugars (and their metabolites) and biomolecules with amino groups, such as proteins. Although increases in and the accumulation of AGEs have been implicated in the onset and exacerbation of l...

Aim】 The role of tumor necrosis factor (TNF)-α in angiogenesis was first reported in 1987 in a rat corneal model, but the exact mechanism is not fully understood. In this study, we investigated the mechanism of TNFα-induced tube formation in human endothelial cells. 【Method】 The mechanism of TNFα-induced tube formation was analyzed by the Matrigel...

A prolonged exposure of reducing sugar to protein leads to a non-enzymatic reaction called the Maillard reaction and results in the production of advanced glycation end products (AGEs). AGEs consist of heterogeneous compounds, and AGEs are produced by the reaction of proteins with various types of reacting carbonyl compound. We have previously demo...

Histidine-rich glycoprotein (HRG) is a plasma glycoprotein present in blood at a concentration of approximately 1 µM. It is known to have various physiological activities related to the homeostasis of the coagulation-fibrinolytic system, the immune system, and the blood vascular system, and until now, its effects on monocytes, lymphocytes, and plat...

Histidine-rich glycoprotein (HRG) has been reported to have regulatory effects on blood coagulation and fibrinolytic systems. In addition to these effects, we found that HRG is a factor that is specifically downregulated in sepsis, and that HRG contributes to the amelioration of sepsis via its effects on maintaining neutrophil morphology and functi...

Cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) composes signal pathway which initiates innate immunity. 2'3'-cyclic GMP-AMP (cGAMP) is enzymatically produced by cGAS and activates several signaling pathway through binding to STING. Accumulating evidence indicates that cGAS-STING signaling play an important role in...

【Aim】 Histamine is well known as an inflammatory mediator whereas little is demonstrated about the mechanism of histamine-induced angiogenesis. The role of histamine in angiogenesis was first reported in 1983 in the chorioallantoic membrane (CAM) assay. Still, the histamine-induced tube formation mechanism has not been investigated with histamine s...

Aims We have previously reported that advanced glycation end products derived from incubation of albumin with glycolaldehyde (glycol-AGE), lead to suppression of the toll-like receptor 4 (TLR4) signaling response to lipopolysaccharide. Glycol-AGE-induced suppression of TLR4 signaling is involved in the downregulation of CD14, which is an adaptor pr...

Background Methylglyoxal (MGO) is a known toxic byproduct of glycolysis, with MGO-induced cytotoxicity believed to contribute to the pathogenesis of several diseases. Glyoxalase I (GLO1) is a key enzyme for eliminating MGO in mammalian cells, therefore, compounds affecting GLO1 activity are potential therapeutic agents for MGO-induced disorders. Pr...

Background We previously reported that advanced glycation endproducts (AGEs) increase the proinflammatory activity of high mobility group box-1 (HMGB1), a representative damage-associated molecular pattern molecule (DAMP), through their direct interaction. This suggested that AGEs activate other DAMPs and led us to search for novel DAMPs capable of...

Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor–neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any...

2'3'-Cyclic GMP-AMP (cGAMP) is derived from cancer cell and activates innate immune response via stimulator of interferon genes (STING) pathway. STING is an endoplasmic reticulum-localized transmembrane protein and associated with regulation of several signaling pathway. STING bound with cGAMP lead to the phosphorylation of TANK-binding kinase 1 (T...

Osteoarthritis (OA) is the most common type of cartilage disease and results from the degradation of the extracellular matrix (ECM) in the joints. Approximately, more than 15 million people suffer from OA in Japan. OA also brings with it an extremely high economic burden due to being the most common form of joint disease. Articular cartilage consis...

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target M...

Toxic advanced glycation end products (toxic AGEs) derived from glycolaldehyde (AGE3) have been implicated in the development of diabetic vascular complications such as retinopathy characterised by excessive angiogenesis. Different receptor types, such as receptor for AGEs (RAGE), Toll like receptor-4 and scavenger receptors, are expressed in endot...

Idiopathic pulmonary fibrosis (IPF) is the most common and most deadly form of interstitial lung disease. Osteopontin (OPN), a matricellular protein with proinflammatory and profibrotic properties, plays a major role in several fibrotic diseases, including IPF; OPN is highly upregulated in patients’ lung samples. In this study, we knocked down OPN...

Advanced glycation end products (AGEs) are biologically reactive compounds associated with diabetic complications and aging-related disorders. Exposure to AGEs in endothelial cells lead to excess angiogenesis, however, molecular mechanisms underlying AGE-elicited angiogenesis remain unclear. Many types of receptors, such as receptor for AGEs (RAGE)...

Hyperglycaemia provides a suitable environment for infections and the mechanisms of glucose toxicity include the formation of advanced glycation end-products (AGEs), which comprise non-enzymatically glycosylated proteins, lipids, and nucleic acid amino groups. Among AGE-associated phenotypes, glycolaldehyde-derived toxic AGE (AGE-3) is involved in...

Inflammation caused-aggrecan degradation is a critical event in the pathogenesis of osteoarthritis (OA). The aggrecanases like a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are assumed to be key players in the aggrecan destruction. To develop the comprehensive therapy method for OA, it is essential to elucidate the acti...

In patients with osteoarthritis (OA), there is a decrease in both the concentration and molecular size of hyaluronan (HA) in the synovial fluid and cartilage. Cell migration-inducing hyaluronidase 1 (CEMIP), also known as hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID), was recently reported as an HA depolymerization-related...

Thoracic aortic dissection (TAD) is a life-threatening vascular disease. We showed that CD44, a widely distributed cell surface adhesion molecule, has an important role in inflammation. In this study, we examined the role of CD44 in the development of TAD. TAD was induced by the continuous infusion of β-aminopropionitrile (BAPN), a lysyl oxidase in...

The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cy...

Hyaluronan is an extracellular matrix component of articular cartilage and has been used to treat patients with osteoarthritis. A disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs) play an important role in cartilage degradation in osteoarthritis. We have previously reported that ADAMTS4 and ADAMTS9 were induced by cytokine sti...

Several research groups demonstrated that 'a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS)'-family proteases play roles in cancer progression. However, the origins and contributions of these proteases are not known. Here, we demonstrate an association between host-produced ADAMTS4 and early-stage tumor growth. Mu...

Background The klotho gene was identified as an “aging-suppressor” gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the...

CT images of thoracic and abdominal aortas in a klotho mutant (kl/kl) mouse after 4 weeks of EPA food. (MOV)

CT images of thoracic and abdominal aortas in a klotho mutant (kl/kl) mouse before control food. (MOV)

CT images of thoracic and abdominal aortas in a klotho mutant (kl/kl) mouse before EPA food. (MOV)

CT images of thoracic and abdominal aortas in a klotho mutant (kl/kl) mouse after 4 weeks of control food. (MOV)

Objective A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), comprise 19 members is a family of peptidases. They have several vital functions in physiological and pathological processes of organisms. ADAMTS-9 has aggrecanolytic activity, and is responsible to degrade mainly aggrecan in articular cartilage. It was known that ad...

Purpose: Chronic inflammation is an important etiological factor in the development of arthritic diseases. Several factors contribute to aggregation of chronic inflammation, including the presence of excess adipose tissue. Methods: The putative induction mechanisms of ADAMTS-5 by resistin were investigated in normal primary human articular chondroc...

Cancer stem cells (CSC) are thought to be a sub-population of cancer cells, which are the main tumorigenic cells in the tumors. Although chemoradiotherapy may kill the majority of rapidly dividing cells, CSC-like cell populations may be left behind due to their low turnover and infrequent cell cycling. In 2007, Prince et al. reported the presence o...

Boric acid is a very common chemical used in a wide variety of applications as well as in medicine. In this study, the usage of boric acid as a potential alternative cancer therapeutic was investigated by examining its effect in head and neck cancer cell line proliferation and tumor suppressor gene expression. Head and neck cancer cell lines UT-SCC...

Elucidation of the causes of inflammation has vital importance to development new approach for the treatment of arthritic diseases. The degradation of aggrecan by upregulated disintegrin and metalloproteinase with trombospondin motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis (RA) and osteoarthritis (OA). Increased...

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix...

MicroRNAs (miRNAs) have been reported as playing important roles in cancer development. miRNAs are potential alternative therapeutic targets for cancer. They are also candidate diagnostic and prognostic indicators of breast cancer. miRNAs are small non-coding RNAs that bind to the 3' untranslated region of target mRNAs and down-regulate their trans...

Purpose: Alzheimer's disease (AD), the most common form of dementia, is an irreversible and progressive neurodegenerative disease that is characterized by the progressive loss of cognitive functions, behavioral and psychological disorders and a decrease in daily routine activities. Among people aged 65 years and over, AD is steadily increasing. Gen...

Background/aim: Alzheimer disease (AD) is triggered by interactions of multiple genetic and environmental factors. The APOE gene E4 allele is the best-known risk factor for AD, yet it represents a small ratio of genetic factors. According to genome-wide association studies, the BIN1 gene is the second important risk factor for AD, following the APO...

Purpose: Chronic inflammation is an important etiological factor in the development of arthritic diseases. Several factors contribute to aggregation of chronic inflammation, including the presence of excess adipose tissue. Methods: The putative induction mechanisms of ADAMTS-5 by resistin were investigated in normal primary human articular chondroc...

Aim: Prostate cancer is the most commonly diagnosed malignancy and the second most common cause of cancer deaths in the Western male population. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) modulate the remodeling of the extracellular matrix (ECM). The imbalance between MMPs and TIMPs may lead to an emergence of pathologi...

The irreversible destruction of extracellular matrix (ECM) components is key process for inflammatory and autoimmune diseases. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), a family of metallopeptidase involve in several physiological and pathological processes including degradation of matrix components. Resistin, an adip...

Examination of Role of ING1 Splicing Variant (p33ING1) in Carcinogenesis and Metastasis of Head and Neck Carcinomas

Purpose: The purpose of this study was to determine the effects of hypericin on MCF-7 (Michigan Cancer Foundation- 7) breast cancer cells, as it is known to exert an antitumor effect on the expression and regulation of ADAMTS1, 3, 10 and the p53 gene in breast cancer cells. Methods: MFC-7 cells were cultured and subjected separately to various d...

The cloning of leptin initiated to explore new functions of adipose tissue. The studies revealed that adipose tissue like endocrine organ involves in critical roles by secreting adipokines. Among them, leptin is the most studied and characterized adipokine, and involves in several pivotal processes including inflammation. The degradation of articul...

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a family of peptidases. They comprise 19 members, and have several vital functions in organism. ADAMTS-9 with aggrecanolytic activity is responsible for the degradation of the articular cartilage components like aggrecan. Adiponectin is the most abundantly secreted adipokine...

Visfatin, characterized in 1994 is an adipokine (adipocytokines). It was secreted by not only visceral adipose tissue but also by several tissues. First, visfatin with insulin-mimetic activity has been implicated in the insulin resistance. Finally, it was understand that visfatin involves in several pathological processes like inflammation. The deg...

Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We...

Visfatin, characterized in 1994 is an adipokine (adipocytokines). It was secreted by not only visceral adipose tissue but also by several tissues. First, visfatin with insulin-mimetic activity has been implicated in the insulin resistance. Finally, it was understand that visfatin involves in several pathological processes like inflammation. The deg...

The cloning of leptin initiated to explore new functions of adipose tissue. The studies revealed that adipose tissue like endocrine organ involves in critical roles by secreting adipokines. Among them, leptin is the most studied and characterized adipokine, and involves in several pivotal processes including inflammation. The degradation of articul...

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a family of peptidases. They comprise 19 members, and have several vital functions in organism. ADAMTS-9 with aggrecanolytic activity is responsible for the degradation of the articular cartilage components like aggrecan. Adiponectin is the most abundantly secreted adipokine...

Acne, a chronic inflammatory skin disease, can be seen at any age but it most often occurs in adolescents and young people. Several factors, including increased sebum production, abnormal cornification of the pilosebaceous units, proliferation of Propionibacterium acne, and extracellular matrix (ECM) remodeling, are thought to be associated with th...

Abstract Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells. In AML, the bone marrow makes many immature cells called blasts, which do not mature and cannot fi ght infections. AML is a heterogeneous neoplasm with several pathological, genetic, and molecular subtypes. Combinations of various doses and schedules of drugs have...

Angiogenesis plays an important role in tumor progression. Several reports have demonstrated that a disintegrin and metalloproteinase with thrombospondin motifs1 (ADAMTS1) inhibited angiogenesis via multiple mechanisms. The aim of this study was to investigate the effect of ADAMTS1 on endothelial cells in vitro and on tumor growth with regard to an...

Epigenetics, proposed by Condrad Hal Waddington at the begining of the 1940 describes heritable changes that affect gene expression without changing DNA sequencing. After researches, it has been found that the epigenetics modifications perform important task in many biological processes and diseases like cancer. In this review we summarize the info...

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an early immediate gene. We have previously reported that ADAMTS1 was strongly induced by hypoxia. In this study, we investigated whether ADAMTS1 promoter-driven reporter signal is detectable by acute hypoxia. We constructed the GFP (green fluorescent protein) expression...

Connective tissue growth factor (CTGF) is a secreted protein that regulates fibrosis. We hypothesized that CTGF is induced in a pressure-overloaded (PO) heart and that blocking the angiotensin II type 1 receptor would reduce CTGF expression. Accordingly, we administered olmesartan and compared its effects with other antihypertensive drugs in a PO h...

Objective Previously we reported an interesting gene that transiently induced in the endothelium in myocardial infarction which may be a hypoxia‐inducible gene expressed by endothelial cells. Its expression was limited to a few hours’ hypoxia. We tested if this switch element (we named this sequence as AHR (Acute hypoxia responsive element) for thi...

We analyzed mutation and expression status of human epidermal growth factor receptor 2 (Her2) in head and neck squamous cell carcinoma (HNSCC) using single strand conformation polymorphism (SSCP) mutation analysis and immunohistochemistry (IHC). Mutations were absent in all 85 cases. Out of 57 cases available for IHC, Her2 protein expression was ne...

Objective: ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs1) is an inflammatory-induced gene. We have previously reported ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether 3’-untranslated region (UTR) affects its mRNA stability. The 3’-UTR ADAMTS1 mRNA contains mult...

Objective: ADAMTS9, known as a cytokine-inducible gene, has binding sites for nuclear factor-κB (NF-κB) in its promoter region. NF-κB dimers bind a family of 9-11 bp of this DNA- binding sites (DNA sequences) known as κB sites. NF-κB is involved in cell proliferation, differentiation and apoptosis by inducing and repressing gene expression. Since i...

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is a member of the matrix metalloproteinase family. We have previously reported that ADAMTS1 was strongly expressed in myocardial infarction. In this study, we investigated whether hypoxia induced ADAMTS1 and investigated its regulatory mechanism. In hypoxia, the expression...

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue...

ADAMTS9 is a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes, with aggrecan-degrading activity. It has also been characterized to be reactive and highly activated ADAMTS by IL-1 beta in both chondrosarcoma cells and human chondrocytes (Demircan et al. Arthritis Rheum 52:1451-1460, 2005). In order to underst...

ADAMTS9 is a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes, with aggrecan-degrading activity. The nuclear factor of activated T cells (NFAT) proteins are a family of transcription factors related to Rel/NFκB family whose activation is controlled by calcineurin. The inhibition of aggrecan degradation likel...

Head and neck squamous cell carcinoma (HNSCC) is a frequently occurring cancer, and despite improvement of its treatment methods, including chemotherapy, radiotherapy, and surgery, the improvement of survival remains poor. Recent advances in molecular biology of human cancer indicated various molecular abnormalities in HNSCC, including activation o...

ADAMTS

SWI/SNF is a multiprotein chromatin remodeling complex important for gene regulation. BRG1 and its close relative BRM, have ATPase activity necessary for transcriptional regulation by conformational change of nucleosomes. Due to this role on gene expression, several members of SWI/SNF complex including BRG1 and BRM function as a tumor suppressor or...

Versican, a large chondroitin sulfate proteoglycan, plays a role in conditions such as wound healing and tissue remodelling. To test the hypothesis that versican expression is transiently upregulated and plays a role in the infarcted heart, we examined its expression in a rat model of myocardial infarction. Northern blot analysis demonstrated incre...

To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene. OUMS-27 cells were stimul...

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue...