Inhibition of LSD۱ by gsk-lsd۱ small molecule inhibitor stimulates fetal hemoglobin in CD۳۴+ cells
- سال انتشار: 1400
- محل انتشار: کنفرانس بین المللی ژنتیک و ژنومیکس انسانی
- کد COI اختصاصی: CHGGE01_203
- زبان مقاله: انگلیسی
- تعداد مشاهده: 90
نویسندگان
Molecular Genetics, Islamic Azad University
Faculty of Biological Science, Tarbiat Moddares University, Tehran, Iran
چکیده
Backgrounds: B-thalassemia and sickle cell disease together include the most common inheriteddiseases. switch from fetal γ globin to β globin genes expression occurs at birth, several adultstageγ globin repressors, such as bcl۱۱a, gata۱ and sox۶ have been identified that interact withrepress the γ globin genes. The strong recent results showed one of the modifying repressor isLSD۱.Materials and Methods: We examined the effects of the GSK-LSD۱ inhibitor concentrations onCD۳۴+ cells are isolated from cord blood. Cell number and viability were determined by trypanblue and flow-cytometric analysis. We treated the cells with ۰, ۰.۵, ۱.۵, and ۵ μm of the gsk-lsd۱inhibitor on days ۴ to ۱۴ of the differentiation culture, and then we performed an analysis of theexpression of LSD۱ and γ globin genes comparable levels throughout differentiation with Real-Time PCR.Results: After treatment GSK-LSD۱ inhibitor at ۰.۵, ۱.۵, and ۵ μm did not alter cell proliferationor viability, but ۵μm gsk-lsd۱ reduced cell proliferation and delayed differentiation withoutaffecting cell viability. In ۱.۵-μm concentration of the gsk-lsd۱ inhibitor, the mean of γ-globinmRNA expression was induced up to ۳۳-fold, we observed a decrease in the LSD۱ mRNAexpression in a ۵-μm concentration of the gsk-lsd۱ inhibitor.Conclusion: Our results indicated that LSD۱ played an important role in γ-globin silencing inadult erythroid cells. Further, the GSK-LSD۱ inhibitor increase concentration of HBF inductionwithin the therapeutic plasma concentration. LSD۱ is a molecular- targeted, promisingtherapeutic epigenetic drugs target for γ-globin induction, can be realized for patients with SCD.کلیدواژه ها
Fetal hemoglobin, Hemoglobinopathies, lsd۱, gsk-lsd۱, Epigenetic drugsاطلاعات بیشتر در مورد COI
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