Abstract:
Serum amyloid A (SAA) is one of the acute phase proteins released primarily from the liver in response to infection, inflammation and trauma. Emerging evidence indicates that SAA may function as a host-derived damage-associated molecular pattern (DAMP) protein to sense danger signals in pregnancy. The plasma SAA levels in maternal circulation are significantly increased in normal parturition, particularly in postpartum, as well as in gestational disorders such as premature preterm rupture of membranes, pre-eclampsia, gestational diabetes, and recurrent spontaneous abortion. It is likely that SAA acts as a non-specific DAMP molecule in response to inflammation and trauma experienced under these conditions. Notably, SAA can also be synthesized locally in virtually all gestational tissues. Within these gestational tissues, under the induction by bacterial products, pro-inflammatory cytokines and stress hormone glucocorticoids, SAA may exert tissue-specific effects as a toll-like receptor 4 (TLR4)-sensed DAMP molecule. SAA may promote parturition through stimulation of inflammatory reactions via induction of pro-inflammatory cytokines, chemokines, adhesion molecules and prostaglandins in the uterus, fetal membranes and placenta. In the fetal membranes, SAA may also facilitate membrane rupture through induction of matrix metalloproteases (MMPs)- and autophagy-mediated collagen breakdown and attenuation of lysyl oxidase-mediated collagen cross-linking. SAA synthesized in extravillous trophoblasts may promote their invasiveness into the endometrium in placentation. Here, we summarized the current understanding of SAA in pregnancy with an aim to stimulate in-depth investigation of SAA in pregnancy, which may help better understand how inflammation is initiated in gestational tissues in both normal and abnormal pregnancies.
摘要:
血清淀粉样蛋白A(SAA)是主要从肝脏释放的急性时相蛋白之一,炎症和创伤。新出现的证据表明,SAA可以作为宿主来源的损伤相关分子模式(DAMP)蛋白来感知怀孕中的危险信号。正常分娩时,母体循环中的血浆SAA水平显着升高,尤其是在产后,以及妊娠疾病,如胎膜早破,先兆子痫,妊娠期糖尿病,和反复自然流产。SAA可能作为响应在这些条件下经历的炎症和创伤的非特异性DAMP分子起作用。值得注意的是,SAA也可以在几乎所有的妊娠组织中局部合成。在这些妊娠组织中,在细菌产物的诱导下,促炎细胞因子和应激激素糖皮质激素,SAA可能作为Toll样受体4(TLR4)感知的DAMP分子发挥组织特异性作用。SAA可能通过诱导促炎细胞因子刺激炎性反应来促进分娩,趋化因子,子宫中的粘附分子和前列腺素,胎膜和胎盘。在胎膜中,SAA还可以通过诱导基质金属蛋白酶(MMP)-和自噬介导的胶原分解以及赖氨酰氧化酶介导的胶原交联的减弱来促进膜破裂。在绒毛外滋养层中合成的SAA可能会促进其在胎盘形成中侵入子宫内膜。这里,我们总结了目前对妊娠期SAA的认识,旨在促进妊娠期SAA的深入研究,这可能有助于更好地了解正常和异常妊娠中妊娠组织的炎症是如何开始的。