于洋洋,华晴,张冬梅,王雅莉,李瓅

• 1:郑州大学第二附属医院妇产科
• 2:郑州大学附属郑州中心医院妇产科

摘要(Abstract)：

目的 探讨纤维连接蛋白1(FN1)在胎儿生长受限（FGR）的作用及其可能机制。方法采用Western blot和实时荧光定量PCR检测15例FGR胎盘组织、15例正常胎盘组织中FN1蛋白和mRNA表达，免疫组织化学染色检测FN1阳性表达率。分别用FN1敲除慢病毒（Si-FN1组）和空载体慢病毒（Si-NC组）感染滋养细胞株HTR-8，采用流式细胞术、Western blot及实时荧光定量PCR验证FN1敲除效率，流式细胞术检测HTR-8细胞周期和凋亡，CCK-8法和细胞划痕实验分别检测细胞增殖和迁移率，Transwell实验检测细胞侵袭和迁移数量，Western blot检测磷脂酰肌醇3-激酶（PI3K）和Akt蛋白表达，并对HTR-8细胞进行RNA转录组测序分析。结果 与正常胎盘组织相比，FGR胎盘组织中FN1蛋白和mRNA表达、阳性表达率均降低（P<0.05或P<0.01）。与Si-NC组相比，Si-FN1组HTR-8细胞中FN1蛋白和mRNA表达降低，细胞增殖、迁移和侵袭减少（P<0.05或P<0.01）;Si-NC组与Si-FN1组细胞周期和细胞凋亡率比较无统计学差异（P>0.05）。KEGG通路富集分析提示PI3K/Akt信号通路可能是FN1调节HTR-8细胞增殖、迁移和侵袭的关键通路。Si-FN1组磷酸化PI3K和磷酸化Akt蛋白表达低于Si-NC组（P<0.05）。结论 FN1低表达于FGR胎盘组织；敲低FN1表达可能通过抑制PI3K/Akt信号通路，减少滋养细胞的增殖、侵袭和迁移。

关键词(KeyWords)： 胎儿生长受限;纤维连接蛋白1;滋养细胞;细胞侵袭;细胞迁移

Abstract:

Keywords:

基金项目(Foundation): 河南省科技攻关项目（242102310008）;; 河南省高等学校重点科研项目计划（24A320037）

作者(Author): 于洋洋,华晴,张冬梅,王雅莉,李瓅

DOI: 10.19460/j.cnki.0253-3685.2025.09.006

参考文献(References)：

• [1]陈瑞欣,漆洪波,刘兴会.2021年美国妇产科医师协会胎儿生长受限指南解读[J].实用妇产科杂志,2021,37(12):907-909.
• [2]焦立媛,王华,武硕.胎儿生长受限的病因研究进展[J].国际妇产科学杂志,2018,45(1):10-13.
• [3]李佳雯,郑小敏,应豪,等.妊娠期高血压疾病与胎儿生长受限的相关性研究[J].国际妇产科学杂志,2021,48(2):182-185.
• [4]阮灵灵,刘太行,吴芝红,等.PPBP基因通过调控滋养细胞融合参与胎儿生长受限的发生[J].中国细胞生物学学报,2021,43(5):1029-1040.
• [5]徐叶红,肖景华,李金鸽.HMGB3对胎儿生长受限患者胎盘滋养层细胞增殖及凋亡的影响与机制分析[J].长春中医药大学学报,2021,37(1):139-144.
• [6]ADU-GYAMFI E A,CZIKA A,GORLEKU P N,et al.Theinvolvement of cell adhesion molecules,tight junctions,and gap junctions in human placentation[J].Reprod Sci,2021,28(2):305-320.
• [7] LYALL F,ROBSON S C,BULMER J N.Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction:relationship to clinical outcome[J].H ypertension,2013,62(6):1046-1054.
• [8]曾珊珊,陈敦金,陈兢思,等.妊娠期子宫螺旋动脉重塑异常与妊娠并发症的研究进展[J].国际妇产科学杂志,2021,48(4):376-379.
• [9]XU T P,HUANG M D,XIA R,et al.Decreased expression of the long non-coding RNA FENDRR is associated with poor prognosis in gastric cancer and FENDRR regulates gastric cancer cell metastasis by affecting fibronectinl expression[J].J Hematol Oncol,2014,7:63.
• [10]CHEN Z,TAO Q,QIAO B,et al.Silencing of LINC01116suppresses the development of oral squamous cell carcinoma by up-regulating microRNA-136 to inhibit FN1[J].Cancer Manag Res,2019,11:6043-6059.
• [11] HU A Q,LI Z,ZHOU Y,et al.Single-cell RNA sequencing reveals association of aberrant placental trophoblasts and FN1reduction in late-onset fetal growth restriction[J].Placenta,2024,146:30-41.
• [12]MEZZENGA R,MITSI M.The molecular dance of fibronectin:conformational flexibility leads to functional versatility[J].Biomacromolecules,2019,20(1):55-72.
• [13]瞿琳,周欣,孙丽洲.不明原因绒毛炎致滋养细胞凋亡在胎儿生长受限发病中的作用[J].国际妇产科学杂志,2022,49(4):415-419.
• [14] KN?FLER M,HAIDER S,SALEH L,et al.Human placenta and trophoblast development:key molecular mechanisms and model systems[J].Cell Mol Life Sci,2019,76(18):3479-3496.
• [15]白新久,刘晓清,王慧,等.胎儿生长受限胎盘因子的研究进展[J].中国妇幼保健,2023,38(3):579-582.
• [16]BORG A J,YONG H E,LAPPAS M,et al.Decreased STAT3in human idiopathic fetal growth restriction contributes to trophoblast dysfunction[J].Reproduction,2015,149(5):523-532.
• [17]HOU J,LI L,ZHU H,et al.Association between breast cancer cell migration and radiosensitivity in vitro[J].Oncol Lett,2019,18(6):6877-6884.
• [18]ZHANG S,WANG Q,HAN Q,et al.Identification and analysis of genes associated with papillary thyroid carcinoma by bioinformatics methods[J].Biosci Rep,2019,39(4):BSR20190083.
• [19]CAI X,LIU C,ZHANG T N,et al.Down-regulation of FN1inhibits colorectal carcinogenesls by suppressing proliferation,migration,and invasion[J].J Cell Biochem,2018,119(6):4717-4728.
• [20]WU C,ZENG M H,LIAO G,et al.Neuropilin-1 interacts with fibronectin-1 to promote epithelial-mesenchymal transi-tion progress in gastric cancer[J].Onco Targets Ther,2020,13:10677-10687.
• [21]PAN S,ZHU J,LIU P,et al.FN1 mRNA 3'-UTR supersedes traditional fibronectin 1 in facilitating the invasion and metastasis of gastric cancer through the FN1 3'-UTR-let-7i-5pTHBS1 axis[J].Theranostics,2023,13(14):5130-5150.
• [22]DING Y,PAN Y,LIU S,et al.Elevation of MiR-9-3p suppresses the epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via down-regulating FN1,ITGB1 and ITGAV[J].Cancer Biol Ther,2017,18(6):414-424.
• [23]LIAO Y X,ZHANG Z P,ZHAO J,et al.Effects of fibronectinl on cell proliferation,senescence and apoptosis of human glioma cells through the PI3K/AKT signaling pathway[J].Cell Physiol Biochem,2018,48(3):1382-1396.
• [24]JI J,CHEN L,ZHUANG Y,et al.Fibronectin 1 inhibits the apoptosis of human trophoblasts by activating the PI3K/Akt signaling pathway[J].Int J Mol Med,2020,46(5):1908-1922.
• [25]ZHANG C,LIANG R,GAN X,et al.MicroRNA-384-5p/Beclin-1 as potential indicators for epigallocatechin gallate against cardiomyocytes ischemia reperfusion injury by inhibiting autophagy via PI3K/Akt pathway[J].Drug Des Devel Ther,2019,13:3607-3623.
• [26]刘运华,赵宗江,张新雪,等.派特灵对HeLa细胞增殖迁移能力及PI3K/Akt信号转导通路的影响[J].中国实验方剂学杂志,2020,26(17):56-63.
• [27]潘欢.eEF1A2和PI3 K-Akt信号途径的相关基因在宫颈癌中表达的意义[D].新疆:石河子大学,2016.
• [28]SHAO H,MOHAMED E M,XU G G,et al.Carnitine palmitoyltransferase 1A functions to repress FoxO transcription factors to allow cell cycle progression in ovarian cancer[J].Oncotarget,2016,7(4):3832-3846.
• [29]LV C L,ZHANG T,YAN T Z,et al.MicroRNA-448 inhibits the regeneration of spinal cord injury through PI3K/AKT/Bcl-2 axis[J].Eur Rev Med Pharmacol Sci,2019,23(7):2719-2726.