คลังข้อมูลการวิจัยการเกษตรไทย

ผู้แต่ง Chokdee Wongborisuth

เผยแพร่โดย

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

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งานวิจัยที่แนะนำ Phylogenetic analysis reveals two morphologically unique new species in the genera Astrochapsa and Nitidochapsa (lichenized Ascomycota : Graphidaceae) Liver disease burden and required treatment expenditures for hepatitis C virus (HCV) infection in Thailand: Implications for HCV elimination in the new therapeutic era, a population-based study Development of fetal hemoglobin inducers from medicinal plants for the clinical management of beta-thalassemia Comparative efficacy of different treatment protocols in therapeutic management of leukoderma in buffaloes (Buffalo Bulletin (Thailand),36(4)) Twenty-three new species in the lichen family Graphidaceae from New Caledonia (Ostropales, Ascomycota) PERFORMANCE OF TREATMENT OF RUBBER PROCESS EFFLUENTS BY ANAEROBIC – AEROBIC TREATMENT PLANTS IN SRI LANKA Occurrence and efficacy of bisphenol A (BPA) treatment in selected municipalwastewater treatment plants, Bangkok, Thailand Chelonopsis thailandica, a new species and new record of Chelonopsis (Lamiaceae) from Thailand New locality record for Haplorchoides mehrai and possible interactions with Opisthorchis viverrini metacercariae in cyprinid fishes in Northeast Thailand Comparative therapeutic efficacy of homeopathic complex, herbal extract and antibiotic in the treatment of subclinical mastitis in dairy buffaloes (Buffalo Bulletin,37(2))

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ชื่อเรื่อง (EN):	ZNF802 (JAZF1), a possible new therapeutic target for treatment of beta-thalassemia
ผู้แต่ง / หัวหน้าโครงการ (EN):	Chokdee Wongborisuth
บทคัดย่อ (EN):	b-Thalassemias are groups of inherited blood disorders caused by reduced or absent production of b-globin chains of adult hemoglobin (HbA; a2b2). The severely affected patients with b-thalassemia require lifelong blood transfusion and chelation therapy. Reactivation of fetal hemoglobin (HbF; a2g2) could ameliorate the symptoms of patients via increased total hemoglobin production and reduced imbalanced a- to non-a-globin synthesis. Hemoglobin switching during human development requires activities of several transcription factor proteins, including those bind to the globin gene promoters. However, the regulation of fetal to adult hemoglobin switching is not fully understood. Previously, we have carried out the microarray analysis comparing human erythroblasts derived from therapeutic aborted fetal liver and adult peripheral blood. The results showed that ZNF802 mRNA is among the transcripts that up-regulated in adult erythroblast of greater than 2-fold change. ZNF802, also called JAZF1, is a 27 kDa protein containing two zinc finger motifs that acting as transcriptional repressor by binding to the direct repeat (DR) elements on DNA. In this study, quantitative RT-PCR was performed in order to validate the microarray data. We observed 13-fold up-regulation of ZNF802 in adult erythroid cells compared to those cells derived from fetal liver. To further elucidate the role of ZNF802 in reduction of HbF expression in adult erythroids, the lentivirus carrying ZNF802 specific shRNA and non-targeted shRNA were designed and constructed for transduction in erythroblasts. Hematopoietic CD34+ progenitor cells were isolated from b-thalassemia/HbE patients (n=9) and subjected to ex vivo two-phase liquid erythroid culture. The results showed the reduction of greater than 90% of ZNF802 transcript and nearly undetectable level of ZNF802 protein in cells transduced with the ZNF802 shRNA lentivirus. As expected, the level of g-globin transcript and levels of HbF were increased in ZNF802 knockdown erythroid cells in b-thalassemia/HbE (5-fold changed and HbF 26.9±7.4% vs 18.5±6.8% in non-targeted shRNA (p-value = 0.04), respectively). Interestingly, we found up-regulation of the embryonic e-globin and z-globin transcripts in knockdown ZNF802 cells compared to non-targeted shRNA control (15-fold and 10-fold changed (p-value = 0.01), respectively). To note, the diminishing of ZNF802 effect on the proliferation and differentiation pattern of erythriod cells was not found. Altogether, our findings suggested that ZNF802 may play a role as the transcriptional repressor of g-globin gene in human adult erythroid cells, thus served as a possible new therapeutic target for treatment of b-thalassemia. The molecular mechanisms underlying the ZNF802 mediated HbF reduction are underway.
บทคัดย่อ:	ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN):	en
เอกสารแนบ (EN):	http://nih.dmsc.moph.go.th/research/showimgdetil.php?id=699
เผยแพร่โดย (EN):	1 Program in Molecular Medicine, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand 2 Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 3 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 4 Section of Translational Medicine, Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 5 National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand
คำสำคัญ (EN):	ZNF802
เจ้าของลิขสิทธิ์ (EN):	National Institute of Health, Department of Medical Science