Hyaluronan up-regulates growth and invasion of trophoblasts in an autocrine manner via PI3K/AKT and MAPK/ERK1/2 pathways in early human pregnancy
Hyaluronan up-regulates growth and invasion of trophoblasts in an autocrine manner via PI3K/AKT and MAPK/ERK1/2 pathways in early human pregnancy
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在人类妊娠早期，透明质酸通过 PI3K/AKT 和 MAPK/ERK1/2 途径以自分泌方式上调滋养层细胞的生长和侵袭
DOI：
10.1016/j.placenta.2013.05.009
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发表时间：
2013-09-01
期刊：
影响因子：
3.8
通讯作者：
Li, D-J.
中科院分区：
文献类型：
--
作者：
Zhu, R.;Huang, Y-H.;Li, D-J.
前言：透明质酸（HA）作为人类孕体细胞外基质的关键分子之一，一直受到人们的关注。方法：采用免疫组化法和实时荧光定量RT-PCR法分别检测正常妊娠和流产胎盘组织中HA和HA合成酶（HA synthetase，HAS）的表达。ELISA法检测原代滋养细胞分泌HA的情况。观察HA对滋养细胞增殖、凋亡及侵袭力的影响。结果：正常早孕绒毛组织中HAS 2的表达和HA的分泌均高于流产绒毛组织，且原代滋养细胞持续分泌HA。高分子量HA（HMW-HA）和中分子量HA（MMW-HA）促进滋养细胞增殖和侵袭，抑制细胞凋亡。而低分子量HA对人滋养层细胞的生长和侵袭能力无明显影响。此外，HMW-HA对滋养细胞生长的促进作用强于MMW-HA，而MMW-HA对滋养细胞侵袭力的促进作用强于HMW-HA。HMW-HA激活滋养细胞PI 3 K/AKT和MAPK/ERK 1/2信号通路。阻断PI 3 K/AKT或MAPK/ERK 1/2信号通路可抑制HA上调的滋养细胞生长和侵袭能力。结论：高水平、大分子量的HA可促进滋养细胞自分泌生长和侵袭，有利于胎盘形成和早孕的维持。(C)2013爱思唯尔有限公司保留所有权利。
Introduction: As one of the key molecules in the extracellular matrix in human conceptus, hyaluronan (HA) has been receiving particular attention. Here, we have investigated the expression and regulation of different molecular weight HA on the biological behaviors of primary human trophoblasts during the first trimester of pregnancy.Methods: The expression of HA and HA synthetase (HAS) by human first trimester trophoblasts was analyzed in placentae from normal pregnancy or miscarriage by immunochemistry and real-time RT-PCR, respectively. ELISA was used to measure the secretion of HA by primary trophoblasts. The effects of HA on the proliferation, apoptosis and invasiveness of trophoblasts were examined. We also investigated the signaling pathways involved in HA activation in human trophoblasts.Results: The higher HAS2 expression and HA secretion were observed in normal villi than that of miscarriage, and the primary trophoblasts secreted HA continuously. High molecular weight HA (HMW-HA) and medium molecular weight HA (MMW-HA) promoted proliferation and invasiveness while inhibited apoptosis of trophoblasts. However, low molecular weight HA (LMW-HA) had no obvious effect on the growth or invasiveness of human trophoblasts. In addition, HMW-HA showed more efficiently than MMW-HA on the growth while MMW-HA displayed a more obvious effect on the invasiveness of trophoblasts than HMW-HA. HMW-HA activated PI3K/AKT and MAPK/ERK1/2 signaling pathways in trophoblasts. Blocking PI3K/AKT or MAPK/ERK1/2 signaling inhibited the HA-upregulated growth and invasiveness of human trophoblasts.Conclusion: Our results suggest that higher level and greater molecular mass of HA can promote trophoblast growth and invasion in an autocrine manner, which was beneficial to placentation and maintenance of human early pregnancy. (C) 2013 Elsevier Ltd. All rights reserved.