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Dual roles of telomerase in cardiac protection and repair

机译:心脏保护和修复中端粒酶的双重作用

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Together, the limited capacity for regenerative growth in cardiac muscle after injury and the prevalence of ongoing sporadic cell death due to apoptosis in chronic heart failure states pose one of the paramount challenges in heart failure therapeutics. In adults, the unique self-renewal potential of progenitor/stem cells is associated with telomerase reverse transcriptase (TBRT), an RNA-dependent DNA polymerase that maintains the lariat-like loop capping chromosome ends. We have identified telomere uncapping, mediated by down-regulation of telomere repeat-binding factor 2 (TRF2) as a novel trigger of cell death in human dilated cardiomyopathy. Conversely, we identified a residual TERT+ population in adult myocardium, as a potential source of cardiac progenitor cells. Residual TERT expression was localized to cells expressing stem cell antigen 1 (Sca1). Cardiac-resident Sca1~+ cells lack haematopoietic stem cell markers and transcripts for cardiac structural genes, yet express many cardiogenic transcription factors. If given intravenously to mice just after ischemia-reperfusion injury, cardiac Sca1~+ cells home selectively to injured myocardium and differentiate spontaneously in situ.
机译:在一起,损伤后心肌肌肉再生生长的能力有限,慢性心力衰竭凋亡导致的散发性细胞死亡的患病率为心力衰竭治疗症的最重要挑战之一。在成人中,祖母/干细胞的独特自我更新潜力与端粒酶逆转录酶(TBRT),一种RNA依赖性DNA聚合酶,其维持Lariat样环覆盖染色体末端。我们已经鉴定了以端粒重复结合因子2(TRF2)的降低调节介导的端粒凋亡,作为人扩张心肌病的细胞死亡的新触发。相反,我们鉴定了成人心肌中的残留叔+群,作为心脏祖细胞的潜在来源。将残留的TERT表达定位于表达干细胞抗原1(SCA1)的细胞。心脏植物SCA1〜+细胞缺乏血液结构基因的血液吞咽干细胞标记物和转录物,但表达了许多心形成转录因子。如果在缺血再灌注损伤后静脉内给予小鼠,则心脏SCA1〜+细胞家庭选择性地造成伤害心肌,并自发地分化原位。

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