Researcher: Gökyüzü, Aysu Bilge
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Gökyüzü, Aysu Bilge
Yılmaz, Aysu Bilge
Yılmaz, Aysu Bilge
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Publication Metadata only Suppressor effects of sodium pentaborate pentahydrate and pluronic F68 on adipogenic differentiation and fat accumulation(Humana Press Inc, 2020) Tapsin, Sidika; Elbasan, Elif Burce; Kayhan, Hatice Damla; Sahin, Fikrettin; Turkel, Nezaket; N/A; Gökyüzü, Aysu Bilge; PhD Student; N/A; N/AObesity is a major public health problem worldwide and a risk factor for certain diseases, including cardiovascular disease, diabetes, cancer, and depression. Unfortunately, currently available anti-obesity drugs have failed in the long-term maintenance of weight control. It has been a challenge to design novel drugs that could potentially treat obesity or prevent uncontrolled weight-gain which lies underneath the pathology of obesity. Since obesity in a way is a consequence of the accumulating new mature adipocytes from undifferentiated precursors which is a process also termed as adipogenesis, drugs that might control adipogenesis could be beneficial for the treatment of obesity. In the current study, combined effect of sodium pentaborate pentahydrate (NaB) and pluronic F68 on adipogenic differentiation was examined by administering various combinations of the two agents to human adipose-derived stem cells (hADSCs) in in vitro. Immunocytochemistry and quantitative RT-PCR were performed to evaluate the levels of adipogenesis-promoting genes such as peroxisome proliferator-activated receptor-gamma (PPAR gamma), fatty acid binding protein (FABP4), and adiponectin. Results indicated that expressions of all these three genes were restrained. Furthermore, Oil Red O staining revealed that lipid vesicle formation was reduced in hADSCs treated with differentiation medium containing NaB/F68 combination. Finally, expression levels of Hippo pathway kinases Lats2, MST1, and scaffold protein Sav1 were reduced in these cells, suggesting a possible link between Hippo pathway-dependent downregulation of PPAR gamma and the NaB/F68 treatment. Herein, we showed that combination of NaB and F68 curtails adipocyte differentiation by inhibiting the adipogenic transcriptional program leading to a decrease in lipid accumulation in adipocytes even at very low doses, thereby uncovered a striking opportunity to use this combination in obesity treatment.Publication Metadata only The role of pericytes in the pathophysiology multiple of sclerosis(Lippincott Williams & Wilkins, 2019) Tüzün, Erdem; Ulusoy, Canan; Küçükali, Cem; Şekerdağ, Emine; Atak, Dila; Gökyüzü, Aysu Bilge; Zeybel, Müjdat; Çakmak, Özgür Öztop; Vural, Atay; Özdemir, Yasemin Gürsoy; PhD Student; PhD Student; PhD Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; School of Medicine; School of Medicine; School of Medicine; N/A; N/A; N/A; 214694; 299358; 182369; 170592Objective: Our aim was to investigate the impact of pericytes, an important component of the blood brain barrier (BBB), on multiple sclerosis (MS) pathogenesis. Background: Although MS is known as a classical inflammatory demyelinating disorder, the involvement of glial cells in demyelination is increasingly recognized. Vascular pathology has also been recently found to contribute to the pathogenesis of MS. However, the exact mechanisms of this pathology and the influence of pericytes have been scarcely investigated. Design/Methods: Experimental allergic encephalomyelitis (EAE) was induced in C57BL6 mice by myelin oligodendrocyte glycoprotein (MOG) immunization. BBB permeability, number and localization of pericytes were assessed in MS lesions and extracellular matrix components were investigated by immunohistochemical methods. Results: Multiple inflammatory lesions were detected in spinal cord and brain on 40th day of MOG-induced EAE. The lesions contained an abundance of T cells and macrophages and lacked myelin. The BBB permeability increase was shown on EAE lesions by albumin staining. The lesion sites with albumin leakage showed a reduction in PDGFRB+ pericytes and some of the pericytes were found to deviate from the walls of microvessels and be repositioned in the brain parenchyma. Moreover, aSMA+ cells and the extracellular matrix protein content around PDGFRB+ and aSMA+ cells were significantly increased. Conclusions: In this study, we have shown for the first time that EAE lesions show altered pericyte distribution. This alteration is associated with a change in BBB permeability and an increase in extracellular matrix.Publication Open Access Impact of autoimmune demyelinating brain disease sera on pericyte survival(Turkish Neuropsychiatry Association / Türk Nöropsikiyatri Derneği, 2021) Ulusoy, Canan; Yılmaz, Vuslat; Küçükali, Cem İsmail; Karaaslan, Zerrin; Kürtüncü, Murat; Türkoğlu, Recai; Tüzün, Erdem; Şekerdağ, Emine; Gökyüzü, Aysu Bilge; Atak, Dila; Vural, Atay; Özdemir, Yasemin Gürsoy; PhD Student; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; 182369; 170592Introduction: multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination and brain pericyte dysfunction might be involved in MS pathogenesis Our aim was to evaluate whether the factors in serum affect pericyte survival. Method: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce experimental autoimmune encephalomyelitis (EAE). To confirm the animal model, the sera level of anti-MOG antibody in mice and platelet-derived growth factor-BB (PDGF-BB) in patients was measured by ELISA. Human brain vascular pericytes (HBVP) cell lines were incubated with sera of EAE mice and primer progressive MS (PPMS), seconder progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients. The viability of HBVP is measured with Annexin V-FITC/propidium iodide staining with flow cytometry. Results: annexin V-FITC/propidium iodide staining with flow cytometry showed increased ratios of early apoptosis and decreased survival following incubation with sera of EAE and progressive MS. Levels of platelet-derived growth factor-BB were identical in serum and cerebrospinal fluids of patients with different forms of MS. Conclusion: our results suggest that serum factors might contribute to progressive MS pathogenesis via pericyte dysfunction. / Amaç: multipl skleroz (MS) merkezi sinir sisteminin (MSS) otoimmün demiyelinizan hastalığıdır. Son yıllardaki bulgular beyin perisit disfonksiyonunun MS patogenezinde yol oynayabileceğini göstermiştir. Bu çalışmada amacımız MS’nin perisit sağkalımına etkilerini ortaya koymaktır. Yöntem: MS hayvan modeli olan deneysel otoimmün ensefalomiyelit (DOE) modelini oluşturmak için, 8–10 haftalık C57BL/6 dişi fareler miyelin oligodendrosit glikoprotein (MOG) ile immünize edildi. Deneysel hayvan modelinin başarılı bir şekilde oluştuğunu doğrulamak için fareler klinik olarak gözlemlendi ve kanları alınarak serumlarında anti-MOG antikoru taraması yapıldı. Hücre kültürü ortamında, insan beyin damarsal perisit (İBDP) ile DOE fare ve insan MS hastası serumları (yineleyici MS, sekonder progresif MS ve primer progresif MS hastaları dâhil edilmiştir.) Yirmi dört saat inkübe edildi. Perisitlerin hücresel canlılık durumu Annexin V-FITC/ propidiyum iyodid (PI) ile akım sitometrisinde değerlendirildi. Ayrıca MS hastaları serumunda perisitlerin fonksiyonu için önemli olan trombosit kaynaklı büyüme faktörü düzeyi ELISA yöntemi ile ölçüldü. Bulgular: DOE ve progresif tip MS serumları ile inkübe olan perisitlerin diğer gruplara göre anlamlı derecede yüksek oranlarda erken apoptoza girdiği ve buna bağlı olarak canlılık yüzdelerinin düştüğü görülmüştür. Farklı MS tiplerine sahip hasta ve sağlıklı kontrollerin serum ve beyin omurilik sıvılarındaki trombosit-kaynaklı büyüme faktörü seviyeleri açısından anlamlı bir fark bulunmadı. Sonuç: elde ettiğimiz bulgular progresif tip MS hastalarının serumlarındaki birtakım faktörlerin perisit disfonksiyonuna sebep olarak MS patogenezine katkı yaptığını düşündürmektedir.Publication Open Access The role of pericytes in the pathophysiology multiple of sclerosis(Lippincott Williams and Wilkins (LWW), 2019) Tüzün, Erdem; Ulusoy, Canan; Küçükali, Cem; N/A; N/A; Şekerdağ, Emine; Atak, Dila; Gökyüzü, Aysu Bilge; Zeybel, Müjdat; Çakmak, Özgür Öztop; Özdemir, Yasemin Gürsoy; Vural, Atay; PhD Student; Researcher; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; N/A; N/A; 214694; N/A; 170592; 182369