คลังข้อมูลการวิจัยการเกษตรไทย

ผู้แต่ง Sukanya Chumchuen

เผยแพร่โดย

1 Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 2 Program in Molecular Medicine, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand 3 Department of Forensic Science, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, Thailand 4 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 5 National Institute of Health, Department of Medical Science, Ministry of Public Health

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งานวิจัยที่แนะนำ Expansion of rubber plantations as an environment factor to increase malaria risk at the Thai borders UNC0638 induces high levels of fetal hemoglobin expression in β-thalassemia/HbE erythroid progenitor cells Histone modification levels in β-thalassemia/hemoglobin E erythroid cells Development of fetal hemoglobin inducers from medicinal plants for the clinical management of beta-thalassemia Comparison of gene expression profiles between human erythroid cells derived from fetal liver and adult peripheral blood Cloning and expression of HbACO2 of Hevea brasiliensis Expression of NAC Transcription Factor under Drought Stress in Hevea brasiliensis Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet activation in hemoglobin E/ß-thalassemia subjects Cloning and expression of 3-hydroxy-3-methylglutaryl-Coa Reductase 1 (Hmge 1) from Hevea brasiliensis High-level induction of fetal haemoglobin by pomalidomide in β-thalassaemia/HbE erythroid progenitor cells

คัดลอก URL

ชื่อเรื่อง (EN):	Downregulation of transcription factor LRF/ZBTB7A increases fetal hemoglobin expression in -thalassemia/hemoglobin E erythroid cells
ผู้แต่ง / หัวหน้าโครงการ (EN):	Sukanya Chumchuen
บทคัดย่อ (EN):	LRF/ZBTB7A is a transcription factor that has been recently identified as a new key regulator of fetal hemoglobin (HbF; a2g2) production in erythroid cells. Reduction of LRF/ZBTB7A expression led to increases in levels of HbF in human CD34+ hematopoietic stem and progenitor cell (HSPC)-derived erythroblast and in human immortalized erythroid line (HUDEP-2). Since reactivation of g-globin gene is associated with the improvement of clinical manifestations of b-hemoglobinopathy patients, decrement in LRF/ZBTB7A expression might be a substantial interest as a novel target for gene therapy in b-thalassemia. In this study, we investigated the effects of LRF/ZBTB7A downregulation in erythroid cells derived from b-thalassemia/HbE patients in order to evaluate its therapeutic potential. The hematopoietic CD34+ progenitor cells were collected from 3 patients and 3 healthy normal individuals' peripheral blood and subjected for in vitro erythroblast culture. The cells were transduced with lentivirus carrying LRF/ZBTB7A specific shRNA, and used untransduced cells and non-targeted control shRNA (shNTC) as experimental controls. The LRF/ZBTB7A shRNA reduced LRF/ZBTB7A transcript and protein to nearly undetectable levels. Interestingly, downregulation of LRF/ZBTB7A increased expression of g-globin, e-globin and z-globin in both adult normal and b-thalassemia/HbE derived cells, whereas a-globin, b-globin and d-globin expression were decreased. As previously reported, we found that the LRF/ZBTB7A knockdown produced a robust increase in HbF levels in both normal (43.3±9.0% vs. 5.9±2.1% in shNTC) and b-thalassemia/HbE erythroblasts (78.1±3.5% vs. 26.3±3.9% in shNTC). Noteworthy, the delay of erythroid differentiation was observed in the LRF/ZBTB7A knockdown cells of both derived from b-thalassemia/HbE patients and normal control, suggesting an additional role of LRF/ZBTB7A in regulating erythroid maturation. These data support the manipulation of LRF/ZBTB7A as one of the most interesting gene therapy candidates for treating the b-thalassemia, but the effect on erythroid cell maturation is needed to be concerned and required further investigation.
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ภาษา (EN):	en
เอกสารแนบ (EN):	http://nih.dmsc.moph.go.th/research/showimgdetil.php?id=700
เผยแพร่โดย (EN):	1 Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 2 Program in Molecular Medicine, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand 3 Department of Forensic Science, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, Thailand 4 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 5 National Institute of Health, Department of Medical Science, Ministry of Public Health
คำสำคัญ (EN):	ZBTB7A
เจ้าของลิขสิทธิ์ (EN):	National Institute of Health, Department of Medical Science