Novel regulation of human myometrial contractility by histone deacetylase 8 (HDAC8)

大约6%-10%的人类怀孕在足月之前分娩结束，早产儿遭受长期的身体和精神残疾。此外，高达65%的围产儿与早产有关。到目前为止，用于停止宫缩的药物，称为宫缩解药，仍然不够有效和安全，对母亲和婴儿都会产生非特异性的副作用，而且往往是危险的副作用。最近对血管平滑肌细胞的研究表明，一种特定的蛋白质组蛋白脱乙酰基酶8(HDAC8)是一种特异性的平滑肌标志物，对这种类型的肌肉细胞的收缩是必不可少的。我们的初步数据还表明，该蛋白可能在妊娠和分娩期间调节子宫平滑肌活动方面发挥重要作用。因此，研究提案的目的是确定是否如此，并确定高选择性的HDAC8抑制剂是否可以在更好地管理早产方面作为潜在的新型治疗剂。

Approximately 6-10% of human pregnancies end with delivery before ?full term?, and premature born babies suffer from long term physical and mental handicap. Furthermore, up to 65% of perinatal births are related to premature birth. To date, drugs used to stop contractions, termed tocolytics, are still not effective and safe enough and cause non-specific and often dangerous side effects for both mother and infant. Recent investigations on vascular smooth muscle cells has indicated that a specific protein histone deacetylase 8 (HDAC8) is a specific marker of smooth muscle and is essential for the contractility of this muscle cell type. Our initial data also indicates that this protein may play an important role in regulating uterine smooth muscle activity during pregnancy and labour. Consequently the purpose of the research proposal are to define whether this is the case and to determine whether highly selective HDAC8 inhibitors can act as potential novel therapeutic agents in the better management of premature labour.