Downregulation of SPARC expression inhibits the invasion of human trophoblast cells in vitro.
Downregulation of SPARC expression inhibits the invasion of human trophoblast cells in vitro.
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SPARC表达下调抑制体外人滋养层细胞的侵袭
DOI：
10.1371/journal.pone.0069079
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Jiang Y;Zhu Y;Shi Y;He Y;Kuang Z;Sun Z;Wang J
成功的妊娠依赖于绒毛外滋养细胞（EVT）侵入子宫蜕膜的精确调节。糖蛋白（分泌的酸性蛋白，富含半胱氨酸）是一种基质细胞糖蛋白，其在与肥胖和糖尿病相关的病理以及肿瘤发生中起关键作用。本研究的目的是探讨在滋养层细胞侵袭过程中的作用，这与肿瘤细胞的侵袭有许多相似之处。Western blot结果显示，小鼠脑、卵巢和子宫中表达量明显高于其他组织。免疫组织化学分析显示，在围着床期的小鼠子宫中的时空表达。在第8天的着床点，孕激素主要聚集在次级蜕膜区（SDZ）、滋养层细胞和囊胚中。在人胎盘绒毛和滋养层细胞系中也检测到了cDNA 3的表达。在Matrigel侵袭试验中，我们发现SPARC特异性RNA干扰显著降低了人绒毛外滋养层细胞HTR 8/SVneo细胞的侵袭。微阵列分析显示，TNF-α耗竭上调白细胞介素11（IL 11）、KISS 1、胰岛素样生长因子结合蛋白4（IGFBP 4）、I型胶原α 1（COLIA 1）、基质金属肽酶9（MMP 9）的表达，下调绒毛膜促性腺激素（CGA）α多肽、MMP 1、间隙连接蛋白α 1（GJA 1）、基因芯片结果通过qRT-PCR和Western blot进一步验证。目前的数据表明，胎盘素可能通过促进滋养层细胞侵入子宫蜕膜而在正常胎盘形成的调节中发挥重要作用。
Successful pregnancy depends on the precise regulation of extravilloustrophoblast (EVT) invasion into the uterine decidua. SPARC (secreted protein acidic and rich in cysteine) is a matricellular glycoprotein that plays critical roles in the pathologies associated with obesity and diabetes, as well as tumorigenesis. The objective of this study was to investigate the role of SPARC in the process of trophoblast invasion which shares many similarities with tumor cell invasion. By Western blot, higher expression of SPARC was observed in mouse brain, ovary and uterus compared to other mouse tissues. Immunohistochemistry analysis revealed a spatio-temporal expression of SPARC in mouse uterus in the periimplantation period. At the implantation site of d8 pregnancy, SPARC mainly accumulated in the secondary decidua zone (SDZ), trophoblast cells and blastocyst. The expression of SPARC was also detected in human placental villi and trophoblast cell lines. In a Matrigel invasion assay, we found SPARC-specific RNA interference significantly reduced the invasion of human extravilloustrophoblast HTR8/SVneo cells. Microarray analysis revealed that SPARC depletion upregulated the expression of interleukin 11 (IL11), KISS1, insulin-like growth factor binding protein 4 (IGFBP4), collagen type I alpha 1 (COLIA1), matrix metallopeptidase 9 (MMP9), and downregulated the expression of the alpha polypeptide of chorionic gonadotropin (CGA), MMP1, gap junction protein alpha 1 (GJA1), et al. The gene array result was further validated by qRT-PCR and Western blot. The present data indicate that SPARC may play an important role in the regulation of normal placentation by promoting the invasion of trophoblast cells into the uterine decidua.
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影响因子：
8.2
作者：
Hiden, Ursula;Bilban, Martin;Desoye, Gernot
通讯作者：
Desoye, Gernot
影响因子：
3.8
作者：
Dalla-Torre, Cristiane A.;Yoshimoto, Maisa;Lee, Chung-Hae;Joshua, Anthony M.;de Toledo, Silvia R. C.;Petrilli, Antonio S.;Andrade, Joyce A. D.;Chilton-MacNeill, Susan;Zielenska, Maria;Squire, Jeremy A.
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Squire, Jeremy A.
影响因子：
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作者：
Brekken, RA;Puolakkainen, P;Sage, EH
通讯作者：
Sage, EH
影响因子：
3.2
作者：
Gruber, HE;Sage, EH;Hanley, EN
通讯作者：
Hanley, EN
影响因子：
3.8
作者：
Knoefler, M.;Simmons, D. G.;Armant, D. R.
通讯作者：
Armant, D. R.