Placental treatment with insulin-like growth factor 1 via nanoparticle differentially impacts vascular remodeling factors in guinea pig sub-placenta/decidua.
Placental treatment with insulin-like growth factor 1 via nanoparticle differentially impacts vascular remodeling factors in guinea pig sub-placenta/decidua.
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胰岛素样生长因子1纳米颗粒胎盘治疗对豚鼠胎盘下/蜕膜下血管重塑因子有不同影响。
DOI：
10.3389/fphys.2022.1055234
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
临床上，尽管病理生理学可能在妊娠早期就已经确立，但胎儿生长受限（FGR）仅在妊娠后期才能检测到。此外，对于 FGR 尚无有效的子宫内治疗方案。我们开发了一种纳米颗粒，能够以滋养层特异性方式递送人胰岛素样 1 生长因子 (hIGF-1)，从而增加 hIGF-1 的表达。胎盘中的 IGF-1 信号传导调节多种发育过程，包括滋养层侵袭和母体血管重塑，这两者在 FGR 胎盘中都会减弱。我们的目的是确定短期 hIGF-1 纳米颗粒治疗对 FGR 和正常生长条件下胎盘下/蜕膜滋养层信号传导机制的影响。使用 FGR 豚鼠母体营养限制 (MNR) 模型，在妊娠第 30-33 天进行超声引导胎盘内注射 hIGF-1 纳米颗粒，并在 5 天后处死母鼠。将胎盘下/蜕膜组织与胎盘分离以进行进一步分析。 Western blot用于分析ERK/AKT/mTOR信号蛋白（磷酸化Erk（pERK）、磷酸化Akt（pAKT）、raptor、rictor和deptor）的蛋白表达。 qPCR用于分析血管/重塑因子[血管内皮生长因子(Vegf)、胎盘生长因子(Pgf)、血小板源性生长因子(Pdgf))和紧密连接/粘附蛋白(claudin 5 (Cldn5)、p-糖蛋白(Abcb1)、occludin (Ocln)和紧密连接蛋白1 (Zo1)]的基因表达。MNR降低了pERK、 PdgfB 和 Cldn5，以及胎盘下/蜕膜中 Ocln 和 Zo1 的表达增加。在 MNR + hIGF1 纳米颗粒胎盘下/蜕膜中，PdgfB、Ocln 和 Zo1 的表达正常化，而与 MNR 相比，pAkt、VegfB、Vegf 受体 1 和 PdgfB 受体增加。 pERK、raptor 的表达和 mTOR 抑制剂 deptor 的表达增加与 VegfA、Plgf 和 PdgfB 的表达减少有关。在此我们表明，hIGF-1 纳米颗粒治疗的影响取决于妊娠环境，hIGF-1 纳米颗粒治疗会触发生长因子的表达增加和 EMT 因子的正常化。信号传导和生长因子表达以实现体内平衡。
Clinically, fetal growth restriction (FGR) is only detectable in later gestation, despite pathophysiological establishment likely earlier in pregnancy. Additionally, there are no effective in utero treatment options for FGR. We have developed a nanoparticle to deliver human insulin-like 1 growth factor (hIGF-1) in a trophoblast-specific manner which results in increased expression of hIGF-1. IGF-1 signaling in the placenta regulates multiple developmental processes including trophoblast invasion and maternal vascular remodeling, both of which can be diminished in the FGR placenta. We aimed to determine the effects of short-term hIGF-1 nanoparticle treatment on sub-placenta/decidua trophoblast signaling mechanisms in FGR and under normal growth conditions. Using the guinea pig maternal nutrient restriction (MNR) model of FGR, ultrasound-guided, intra-placenta injections of hIGF-1 nanoparticle were performed at gestational day 30–33, and dams sacrificed 5 days later. Sub-placenta/decidua tissue was separated from placenta for further analyses. Western blot was used to analyze protein expression of ERK/AKT/mTOR signaling proteins (phospho-Erk (pERK), phospho-Akt (pAKT), raptor, rictor and deptor). qPCR was used to analyze gene expression of vascular/remodeling factors [vascular endothelial growth factor (Vegf), placenta growth factor (Pgf), platelet-derived growth factor (Pdgf)) and tight junction/adhesion proteins (claudin 5 (Cldn5), p-glycoprotein (Abcb1), occludin (Ocln) and tight junction protein 1 (Zo1)]. MNR reduced expression of pERK, PdgfB and Cldn5, and increased expression of Ocln and Zo1 in the sub-placenta/decidua. In MNR + hIGF1 nanoparticle sub-placenta/decidua, expression of PdgfB, Ocln and Zo1 was normalized, whilst pAkt, VegfB, Vegf receptor 1 and PdgfB receptor were increased compared to MNR. In contrast, hIGF-1 nanoparticle treatment of normal placentas reduced expression of pERK, raptor and increased expression of the mTOR inhibitor deptor. This was associated with reduced expression of VegfA, Plgf, and PdgfB. Here we have shown that the impact of hIGF-1 nanoparticle treatment is dependent on pregnancy environment. Under MNR/FGR, hIGF-1 nanoparticle treatment triggers increased expression of growth factors and normalization of EMT factors. However, under normal conditions, the response of the placenta is to decrease AKT/mTOR signaling and growth factor expression to achieve homeostasis.
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影响因子：
3.6
作者：
Chen, Cheng-Yi;Liu, Shu-Hsiang;Chen, Chie-Pein
通讯作者：
Chen, Chie-Pein
影响因子：
4.6
作者：
Depreux, Frederic F.;Czech, Lyubov;Whitlon, Donna S.
通讯作者：
Whitlon, Donna S.
影响因子：
4
作者：
Ikenouchi, J;Matsuda, M;Tsukita, S
通讯作者：
Tsukita, S
DOI：
10.1016/0002-9378(83)90918-3
发表时间：
1983-01-01
影响因子：
9.8
作者：
AHOKAS, RA;ANDERSON, GD;LIPSHITZ, J
通讯作者：
LIPSHITZ, J
影响因子：
2.1
作者：
Chakraborty, C;Gleeson, LM;Lala, PK
通讯作者：
Lala, PK