Stromal Cell-Derived Factor 2: A Novel Protein that Interferes in Endoplasmic Reticulum Stress Pathway in Human Placental Cells.
Stromal Cell-Derived Factor 2: A Novel Protein that Interferes in Endoplasmic Reticulum Stress Pathway in Human Placental Cells.
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DOI：
10.1095/biolreprod.115.138164
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发表时间：
2016-08
影响因子：
3.6
通讯作者：
Bevilacqua E
中科院分区：
文献类型：
--
作者：
Lorenzon-Ojea AR;Guzzo CR;Kapidzic M;Fisher SJ;Bevilacqua E
内质网应激是内质网稳态和蛋白质折叠改变的结果。内质网应激启动细胞适应性机制，以挽救细胞稳态，或者，如果这不起作用，则诱导细胞凋亡。我们先前已经证明，小鼠SDF2在内质网中被亚区块化，广泛表达，并与拟南芥的基质细胞衍生因子(SDF)2L1和SDF2样蛋白显示出强烈的相似性，参与伴侣网络和蛋白质折叠的ER蛋白。因此，我们假设SDF2在内质网应激和未折叠蛋白反应中发挥作用。在这项研究中，我们研究了SDF2在人胎盘中的可能作用。SDF2在整个妊娠过程中均有表达，并由多种细胞类型表达。中期妊娠细胞滋养层细胞(CTB)在分化过程中，通过绒毛膜促性腺激素的产生进行监测，显示SDF2蛋白上调。然而，在小于胎龄的新生儿和体外低氧条件下(P≤0.001，2%O2)的胎盘中，SDF2的表达显著减少，这表明与细胞应激有关。内质网应激诱导的细胞-CTB和BeWo-也在不同的时间点显示SDF2下调，强调了这种关系。SDF2下调之后还伴随着结合免疫球蛋白(Bip)表达的增加，BIP是ER蛋白相关的伴侣蛋白，作为错误折叠蛋白的传感器和ER应激细胞生存标记。与此相一致，SDF2 siRNA导致了Bip表达的显著预期。SDF2的下调也干扰了C/EBP同源蛋白的表达，C/EBP是内质网应激过程中最高诱导基因之一。这些发现提示SDF2可能是滋养层细胞在内质网应激下控制细胞存活的重要调节因子。总之，这项研究发现了一个能够干扰ER应激蛋白的新因子，这可能有助于理解与妊娠胎盘相关疾病相关的ER应激。
Endoplasmic reticulum (ER) stress results from changes in ER homeostasis and folding of proteins. ER stress initiates cellular adaptive mechanisms to rescue cell homeostasis or, if that does not work, to elicit apoptosis. We have previously shown that mouse SDF2 is sublocalized in the ER, is ubiquitously expressed, and shows strong similarities with stromal cell-derived factor (SDF) 2L1 and SDF2-like from Arabidopsis, ER proteins involved in chaperone network and protein folding. Thus, we hypothesized that SDF2 plays a role in the ER stress and unfolded protein response. In this study, we investigated the possible role of SDF2 in the human placenta. Expression of SDF2 was present throughout gestation and was expressed by several cell types. Second-trimester cytotrophoblast cells (CTBs) in the differentiation process, monitored through chorionic gonadotropin production, showed upregulation of SDF2 protein. SDF2 expression, however, was significantly diminished in placentas from neonates small for gestational age and in hypoxic in vitro conditions (P ≤ 0.001, 2% O2), suggesting a link with cellular stress. ER stress-induced cells—CTB and BeWo—also showed SDF2 downregulation in different time points, emphasizing this relationship. SDF2 downregulation was also followed by an increase in binding immunoglobulin protein (BiP) expression, an ER protein-associated chaperone acting as a sensor for misfolded proteins and an ER stress cell survival marker. In line with this, SDF2 siRNA resulted in significant anticipation of BiP expression. Downregulation of SDF2 also interfered with C/EBP homologous protein expression, one of the highest inducible genes during ER stress. These findings suggest that SDF2 may be an important regulatory factor by which trophoblast cells can control cell survival under ER stress. In conclusion, this study identifies a novel factor with the ability to interfere with ER stress proteins, which may contribute to the understanding of ER stress associated with placental-related diseases of pregnancy.
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DOI：
10.1177/1933719108322425
发表时间：
2008-11
期刊：
Reproductive sciences (Thousand Oaks, Calif.)
影响因子：
--
作者：
Mikheev AM;Nabekura T;Kaddoumi A;Bammler TK;Govindarajan R;Hebert MF;Unadkat JD
通讯作者：
Unadkat JD
影响因子：
4.4
作者：
Faria, Miriam R.;Hoshida, Mara S.;Bevilacqua, Estela
通讯作者：
Bevilacqua, Estela
影响因子：
3.8
作者：
Hoshida, M. S.;Gorjao, R.;Bevilacqua, E.
通讯作者：
Bevilacqua, E.
影响因子：
82.9
作者：
Iwawaki, T;Akai, R;Miura, M
通讯作者：
Miura, M
DOI：
10.1016/j.preghy.2010.12.002
发表时间：
2011-01
影响因子：
2.2
作者：
Burton, Graham J.;Yung, Hong-Wa
通讯作者：
Yung, Hong-Wa