Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 9Citation - Scopus: 11Mesenchymal Stem Cells From Adipose Tissue Prone To Lose Their Stemness Associated Markers in Obesity Related Stress Conditions(Nature Portfolio, 2024) Al-Sammarraie, Sura Hilal Ahmed; Ayaz-Guner, Serife; Acar, Mustafa Burak; Simsek, Ahmet; Siniksaran, Betuel Seyhan; Bozalan, Habibe Damla; Ozcan, ServetObesity is a health problem characterized by large expansion of adipose tissue. During this expansion, genotoxic stressors can be accumulated and negatively affect the mesenchymal stem cells (MSCs) of adipose tissue. Due to the oxidative stress generated by these genotoxic stressors, senescence phenotype might be observed in adipose tissue MSCs. Senescent MSCs lose their proliferations and differentiation properties and secrete senescence-associated molecules to their niche thus triggering senescence for the rest of the tissue. Accumulation of senescent cells in adipose tissue results in decreased tissue regeneration and functional impairment not only in the close vicinity but also in the other tissues. Here we hypothesized that declined tissue regeneration might be associated with loss of stemness markers in MSCs population. We analyzed the expression of several stemness-associated genes of in vitro cultured MSCs originated from adipose tissue of high-fat diet and normal diet mice models. Since the heterogenous MSCs population covers a small percentage of the pluripotent stem cells, which have roles in proliferation and tissue regeneration, we measured the percentage of these cells via TRA-1-60 pluripotent state antigen. Additionally, by conducting a shotgun proteomic approach using LC-MS/MS, whole cell proteome of the adipose tissue MSCs of high-fat diet and normal diet mice were analyzed and identified proteins were evaluated via gene ontology and PPI network analysis. MSCs of obese mice showed senescent phenotype and altered cell cycle distribution due to a hostile environment with oxidative stress in adipose tissue where they reside. Additionally, the number of pluripotent markers expressing cells declined in the MSC population of the high-fat diet mice. Gene expression analysis evidenced the loss of stemness with a decrease in the expression of stemness-associated genes. Of the proteomic comparison of the normal and the high-fat diet group, MSCs revealed that stemness-associated molecules were decreased while inflammation and senescence-associated phenotypes emerged in obese mice MSCs. Our results showed us that the MSCs of adipose tissue may lose their stemness properties due to obesity-associated stress conditions.Article Citation - WoS: 21Citation - Scopus: 21Investigation of the Influence of High Glucose on Molecular and Genetic Responses: an in Vitro Study Using a Human Intestine Model(BioMed Central Ltd., 2018) Boztepe, Tuğçe; Güleç, ŞükrüBackground: Dietary glucose consumption has increased worldwide. Long-term high glucose intake contributes to the development of obesity and type 2 diabetes mellitus (T2DM). Obese people tend to eat glucose-containing foods, which can lead to an addiction to glucose, increased glucose levels in the blood and intestine lumen, and exposure of intestinal enterocytes to high dietary glucose. Recent studies have documented a role for enterocytes in glucose sensing. However, the molecular and genetic relationship between high glucose levels and intestinal enterocytes has not been determined. We aimed to identify relevant target genes and molecular pathways regulated by high glucose in a well-established in vitro epithelial cell culture model of the human intestinal system (Caco-2 cells). Methods: Cells were grown in a medium containing 5.5 and 25 mM glucose in a bicameral culture system for 21 days to mimic the human intestine. Transepithelial electrical resistance was used to control monolayer formation and polarization of the cells. Total RNA was isolated, and genome-wide mRNA expression profiles were determined. Molecular pathways were analyzed using the DAVID bioinformatics program. Gene expression levels were confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results: Microarray gene expression data demonstrated that 679 genes (297 upregulated, 382 downregulated) were affected by high glucose treatment. Bioinformatics analysis indicated that intracellular protein export (p=0.0069) and ubiquitin-mediated proteolysis (p=0.024) pathways were induced, whereas glycolysis/gluconeogenesis (p<0.0001), pentose phosphate (p=0.0043), and fructose-mannose metabolism (p=0.013) pathways were downregulated, in response to high glucose. Microarray analysis of gene expression showed that high glucose significantly induced mRNA expression levels of thioredoxin-interacting protein (TXNIP, p=0.0001) and lipocalin 15 (LCN15, p=0.0016) and reduced those of ATP-binding cassette, sub-family A member 1 (ABCA1, p=0.0004), and iroquois homeobox 3 (IRX3, p=0.0001). Conclusions: To our knowledge, this is the first investigation of high glucose-regulated molecular responses in an intestinal enterocyte model. Our findings identify new target genes that may be important in the intestinal glucose absorption and metabolism during high glucose consumption.