The 3'-untranslated region of ADAMTS1 regulates its mRNA stability

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 necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'-UTR may regulate the expression of ADAMTS1 mRNA.</p

Neutrophils’ Extracellular Trap Mechanisms: From Physiology to Pathology

Neutrophils are an essential part of the innate immune system and the first line of defense against invading pathogens. They phagocytose, release granular contents, produce reactive oxygen species, and form neutrophil extracellular traps (NETs) to fight pathogens. With the characterization of NETs and their components, neutrophils were identified as players of the innate adaptive crosstalk. This has placed NETs at the center not only of physiological but also pathological processes. Aside from their role in pathogen uptake and clearance, NETs have been demonstrated to contribute to the resolution of inflammation by forming aggregated NETs able to degrade inflammatory mediators. On the other hand, NETs have the potential to foster severe pathological conditions. When homeostasis is disrupted, they occlude vessels and ducts, serve as sources of autoantigens and danger or damage associated molecular patterns, directly damage tissues, and exaggerate complement activity and inflammation. This review focusses on the understanding of NETs from their formation to their functions in both physiological and pathological processes

Association Between Survivin Gene Polymorphisms and the Susceptibility to Colon Cancer Development in the Turkish Population

Ankarali, Handan Camdeviren/0000-0002-3613-0523; Yaykasli, Kursat/0000-0001-7550-6370WOS: 000351055100074PubMed: 25374237Background: Colon cancer is one of the most common cancers worldwide. Apoptosis is a necessary physiological process for cell elimination which is very important both cellular homeostasis and cell proliferation and differantiation. Dysregulation can lead to uncontrolled cell growth and tumor development. Survivin, a member of the IAP family, plays a key role in promotion of cell proliferation as well as inhibition of apoptosis in cancer cells. The aim of this study was to investigate whether specific genetic polymorphisms of survivin could be associated with colon cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between colon cancer risk and survivin gene polymorphisms. Materials and Methods: The relation between colon cancer and survivin -31 G/C (rs9904341), -241 C/T (rs17878467) and -625 C/G (rs8073069) polymorphism in promotor site of survivin gene associated with apoptosis was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Individuals with -31C allele and CC genotype were found to have a higher risk of developing colon cancer (OR=13.4, p=0.01). The -241 CT genotype considerably increased the risk of colon cancer (OR=12.0, p=0.0001). However, there was no significant varaition of the survivin -625 C/G polymorphism among colon cancer patients and controls in our study. Conclusions: This study provides the first evidence that survivin -31 G/C and -241 C/T SNP significantly contribute to the risk of colon cancer in the Turkish population

Erythropoietin stimulates patellar tendon healing in rats

Yaykasli, Kursat/0000-0001-7550-6370; Kandis, Hayati/0000-0001-9151-6050; Kaya, Ertugrul/0000-0003-0081-682XWOS: 000367634100003PubMed: 26067853Backround: Erythropoietin (EPO), regulating erythropoiesis, is used to provide protective and regenerative activity in non-haematopoietic tissues. There is insufficient knowledge about the role of EPO activity in tendon healing. Therefore, we investigated the effect of EPO treatment on healing in rat patellar tendons. Methods: One hundred and twenty-six, four-month-old male Sprague-Dawley rats were randomly assigned to three experimental groups: 1, no treatment; 2, treatment with isotonic saline (NaCl) and 3, treatment with EPO. Each group was randomly subdivided into two groups for sacrifice at three (1a, 2a, 3a) or six weeks (1b, 2b, 3b). Complete incision of the left patellar tendon from the distal patellar pole was performed. We applied body casts for 20 days after the incised edges of the patellar tendon were brought together with a surgical technique. Both legs were harvested and specimens from each group underwent histological, biomechanical, and protein mRNA expression analyses. Results: There were statistically significant differences in the ultimate breaking force between the EPO group and others at both weeks three and six (p<0.05); significant differences in fibroblast proliferation, capillary vessel formation, and local inflammation were found between groups 1 a and 3a, and 2a and 3a (p<0.05). There were statistical differences between la, 3a and 2a, 3a for Col III, TGF-beta 1, and VEGF and between 1b, 3b and 2b, 3b for Col I, Col III, TGF-beta 1, and VEGF mRNA expressions. Conclusion: EPO had an additive effect with surgery on the injured tendon healing process in rats compared to the control groups biomechanically, histopathologically and with tissue protein mRNA expression. (C) 2015 Elsevier B.V. All rights reserved.Duzce University Research FundDuzce University [2012.04.02.91]As a main author I received benefits for this research article by Duzce University Research Fund (project number 2012.04.02.91)