miR⁃15a⁃5p对子痫前期胎盘滋养细胞自噬的影响

doi:10.3969/j.issn.1006-5725.2024.12.004

Abstract

Abstract:

Objective Investigating the impact of miR?15a?5p on autophagy in trophoblast cells of preeclamptic placenta. Methods Collect 20 cases of normal placental tissue and 20 cases of preeclamptic placental tissue from December 2020 to December 2022. Use fluorescence quantitative PCR to detect the expression of miR?15a?5p in placental tissue and trophoblast cells， and study its correlation with patient blood pressure. The HTR8?S/Vneo cells are divided into normal group （control） and hypoxia group， and the effect of hypoxia on the expression of miR?15a?5p is observed. Additionally， mimic?NC group， mimic?NC+hypoxia group， miR?15a?5p mimic group， miR?15a?5p mimic+hypoxia group， inhibitor?NC group， inhibitor?NC+hypoxia group， miR ?15a ?5p inhibitor group， and miR ?15a ?5p inhibitor +hypoxia groups are set up to observe the effect of miR ?15a ?5p on hypoxia?induced autophagy?related proteins LC3B and p62 protein in trophoblast cells. Western blot is used to detect the expression levels of autophagy?related proteins LC3B and p62 protein in each group； TargetScan website predicts the target genes of miR?15a?5p，and detects their expression levels in placental tissue and trophoblast cells. Results Compared with the control group， the expression levels of miR?15a?5p were significantly increased in the placentas and hypoxic trophoblasts of preeclampsia， and they were positively correlated with the blood pressure of the patients. Under hypoxic conditions， the overexpressed miR?15a?5p promoted the protein expression of LC3BII/I， while the relative expression of P62 was decreased. But after interference with miR?15a?5p， LC3BII/I expression was down?regulated and P62 expression was up?regulated. The results of quantitative PCR and Western blot showed that the expression levels of YAP1 in the preeclampsia placental tissues and hypoxic trophoblasts were significantly reduced. Conclusion The upregulation of miR?15a?5p in trophoblast cells of the placenta in individuals with preeclampsia could enhance autophagy in preeclampsia by forming a complex with YAP1.

Key words: preeclampsia, trophoblast, autophagy, miR?15a?5p, YAP1

CLC Number:

R714.25

Sumei YU,Yuyue ZHANG,Liwen MA,Yuanjun KUANG,Qingning CHANG,Min KONG,ZHANG Huiping ZHANGx. Effect of miR⁃15a⁃5p on autophagy of placental trophoblasts in preeclampsia[J]. The Journal of Practical Medicine, 2024, 40(12): 1631-1636.

Figures/Tables 8

Tab.1

Fig.1

Fig.2

Fig.3

Fig.4

Fig.5

Fig.6

Fig.7

References 27

1	RANA S， LEMOINE E， GRANGER J P， et al. Preeclampsia［J］. Circ Res， 2019， 124（7）： 1094⁃1112. doi:10.1161/circresaha.118.313276 doi: 10.1161/circresaha.118.313276
2	冷敏，彭颖，林晓莹，等. 自噬在创面愈合中的作用研究进展［J］. 实用医学杂志， 2020， 36（22）： 3157⁃3165. doi:10.3969/j.issn.1006-5725.2020.22.026 doi: 10.3969/j.issn.1006-5725.2020.22.026
3	冯晓玲，姜天悦，张杨. 胎盘自噬与子痫前期［J］.中国计划生育学杂志， 2022， 30（1）： 236⁃240.
4	KLIONSKY D J， PETRONI G， AMARAVADI R K， et al. Autophagy in major human diseases［J］. EMBO J， 2021， 40（19）：e108863.
5	CORNELIUS D C， WALLACE K. Autophagy in preeclampsia： A new target？［J］. EBioMedicine， 2020， 57：102864. doi:10.1016/j.ebiom.2020.102864 doi: 10.1016/j.ebiom.2020.102864
6	陈国庆，陈璐，曾发，等. 子痫前期孕妇母胎界面炎症介质的表达与线粒体自噬的相关性研究［J］.国际妇产科学杂志， 2020， 47（3）： 271⁃275，361. doi:10.3969/j.issn.1674-1870.2020.03.007 doi: 10.3969/j.issn.1674-1870.2020.03.007
7	CORREIA DE SOUSA M， GJORGJIEVA M， DOLICKA D， et al. Deciphering miRNAs' Action through miRNA Editing［J］. Int J Mol Sci， 2019， 20（24）：6249. doi:10.3390/ijms20246249 doi: 10.3390/ijms20246249
8	ESKANDARI F， REZAEI M， MOHAMMADPOUR⁃GHAREHBAGH A， et al. The association of pri⁃miRNA⁃ 26a1 rs7372209 polymorphism and Preeclampsia susceptibility［J］. Clin Exp Hypertens， 2019， 41（3）： 268⁃273. doi:10.1080/10641963.2018.1469643 doi: 10.1080/10641963.2018.1469643
9	APICELLA C， RUANO C S M， MéHATS C， et al. The Role of Epigenetics in Placental Development and the Etiology of Preeclampsia［J］. Int J Mol Sci， 2019， 20（11）：2837. doi:10.3390/ijms20112837 doi: 10.3390/ijms20112837
10	LAGANà A S， VITALE S G， SAPIA F， et al. miRNA expression for early diagnosis of preeclampsia onset： hope or hype？［J］. J Matern Fetal Neonatal Med， 2018， 31（6）： 817⁃821. doi:10.1080/14767058.2017.1296426 doi: 10.1080/14767058.2017.1296426
11	LV Y， LU C， JI X， et al. Roles of microRNAs in preeclampsia［J］. J Cell Physiol， 2019， 234（2）： 1052⁃1061. doi:10.1002/jcp.27291 doi: 10.1002/jcp.27291
12	SKALIS G， KATSI V， MILIOU A， et al. MicroRNAs in Preeclampsia［J］. Microrna， 2019， 8（1）： 28⁃35. doi:10.2174/2211536607666180813123303 doi: 10.2174/2211536607666180813123303
13	曾带娣，李仲均，萧丽娟，等. 子痫前期患者胎盘中微小RNA⁃34a的表达及相关机制［J］. 发育医学电子杂志， 2020， 8（4）： 329⁃332.
14	潘耀平，桂琦，潘景. 自噬相关蛋白P62、OPTN在重度子痫前期胎盘滋养细胞中的表达及意义［J］.云南师范大学学报（自然科学版）， 2017， 37（3）： 63⁃65.
15	殷荷，王艳华，吴琪瑞，等. miR⁃5088⁃5p在子痫前期患者胎盘组织中的表达及其对滋养细胞自噬的影响［J］.实用医学杂志， 2020， 36（24）： 3312⁃3316，3322.
16	朱亚飞，张玉月，谢琳，等. 环状RNA circ＿BRAF＿2在子痫前期胎盘滋养细胞自噬中的作用［J］.中国临床药理学杂志， 2022， 38（23）： 2860⁃2864.
17	MICHALCZYK M， CELEWICZ A， CELEWICZ M， et al. The Role of Inflammation in the Pathogenesis of Preeclampsia［J］. Mediators Inflamm， 2020， 2020： 3864941. doi:10.1155/2020/3864941 doi: 10.1155/2020/3864941
18	ZHOU W， WANG H， YANG Y， et al. Trophoblast Cell Subtypes and Dysfunction in the Placenta of Individuals with Preeclampsia Revealed by Single⁃Cell RNA Sequencing［J］. Mol Cells， 2022， 45（5）： 317⁃328. doi:10.14348/molcells.2021.0211 doi: 10.14348/molcells.2021.0211
19	GU S， ZHOU C， PEI J， et al. Esomeprazole inhibits hypoxia/endothelial dysfunction⁃induced autophagy in preeclampsia［J］. Cell Tissue Res， 2022， 388（1）： 181⁃194. doi:10.1007/s00441-022-03587-z doi: 10.1007/s00441-022-03587-z
20	GLICK D， BARTH S， MACLEOD K F. Autophagy： cellular and molecular mechanisms［J］. J Pathol， 2010， 221（1）： 3⁃12. doi:10.1002/path.2697 doi: 10.1002/path.2697
21	IVES C W， SINKEY R， RAJAPREYAR I， et al. Preeclampsia⁃Pathophysiology and Clinical Presentations： JACC State⁃of⁃the⁃Art Review［J］. J Am Coll Cardiol， 2020， 76（14）： 1690⁃1702. doi:10.1016/j.jacc.2020.08.014 doi: 10.1016/j.jacc.2020.08.014
22	吴琪瑞，王艳华，柴丽芬，等. circRNA RBM39与miR⁃5088⁃5p在缺氧诱导的滋养细胞自噬中的作用［J］.实用医学杂志， 2020， 36（5）： 570⁃574.
23	ZHANG H， HE Y， WANG J X， et al. miR⁃30⁃5p⁃mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia［J］. Redox Biol， 2020， 29： 101402. doi:10.1016/j.redox.2019.101402 doi: 10.1016/j.redox.2019.101402
24	PENG P， SONG H， XIE C， et al. miR⁃146a⁃5p⁃mediated suppression on trophoblast cell progression and epithelial⁃mesenchymal transition in preeclampsia［J］. Biol Res， 2021， 54（1）： 30. doi:10.1186/s40659-021-00351-5 doi: 10.1186/s40659-021-00351-5
25	ZHOU L， WANG W， WANG F， et al. Plasma⁃derived exosomal miR⁃15a⁃5p as a promising diagnostic biomarker for early detection of endometrial carcinoma［J］. Mol Cancer， 2021， 20（1）： 57. doi:10.1186/s12943-021-01352-4 doi: 10.1186/s12943-021-01352-4
26	KIM M， LY S H， XIE Y， et al. YAP1 and PRDM14 converge to promote cell survival and tumorigenesis［J］. Dev Cell， 2022， 57（2）： 212⁃227.e8. doi:10.1016/j.devcel.2021.12.006 doi: 10.1016/j.devcel.2021.12.006
27	顾天，刘春宏，张飞，等. 大黄素抑制胃癌AGS细胞YAP1、FOXD1基因表达及相关机制［J］. 实用医学杂志， 2024， 40（1）： 59⁃64. doi:10.3969/j.issn.1006-5725.2024.01.011 doi: 10.3969/j.issn.1006-5725.2024.01.011

项目	PC组（n = 20）	PE组（n = 20)	P值
年龄（岁）	30.50 ± 4.861	29.25 ± 4.506	0.404 3
孕周（周）	38.10 ± 2.612	37.82 ± 2.517	0.733 2
收缩压（mmHg）	116.2 ± 9.724	154.3 ± 13.47	< 0.000 1
舒张压（mmHg）	76.80 ± 7.331	103.1 ± 10.43	< 0.000 1
蛋白尿（g/24h）	< 0.3	> 0.3	< 0.05

[1]	Ziling ZENG,Xing WANG,Hongmei TANG,Zhibin WANG,Ning MA,Yuejiao LI,Xiaoyun WANG,Xiefang YUAN,Guofeng XU,Qiaoqiao WANG,Wen ZHANG,Jiayao DUAN,Yun ZHANG. House dust mite⁃induced autophagy affects airway epithelial barrier function through β⁃catenin⁃Snail signaling pathway [J]. The Journal of Practical Medicine, 2025, 41(9): 1309-1318.
[2]	Xu ZHOU,Ranran LU,Fangli REN,Xiaoyu PENG,Xinling. YANG. Effect of EGCG on MPTP⁃induced Parkinson′s model mice via autophagy⁃lysosomal pathway [J]. The Journal of Practical Medicine, 2025, 41(8): 1097-1104.
[3]	Yunting ZHUANG,Yao SONG,Qian CHEN,Yanxuan XIAO,Tian TAN,Wenhui LI,Ruiyan BAI,Zeshan LIN,Zhijian. WANG. Risk factor analysis and predictive indicators of postpartum haemorrhage in singleton pregnant women with severe preeclampsia [J]. The Journal of Practical Medicine, 2025, 41(8): 1155-1160.
[4]	Runfang WANG,Ya DUAN,Liyan DU,Xiaodan LIU,Wenning LIAN,Yan HUO,Dandan. YANG. Epidemiological status and risk factors associated with placental abruption among pregnant women in Hebei Province [J]. The Journal of Practical Medicine, 2025, 41(6): 904-910.
[5]	Zhizhou XIAO,Ying HUANG,Huawei. BIAN. To investigate the effect of aloperine on bone metabolism in osteoporotic mice based on autophagy and apoptosis mediated by Wnt/β⁃catenin signaling pathway [J]. The Journal of Practical Medicine, 2025, 41(4): 500-508.
[6]	Liangxi LU,Haiwang LU,Wenjie WANG,Jun SHI,Zhimin HUANG,Bin BIN. To investigate the mechanism of mitochondrial autophagy regulating the expression of NLRP3 inflammasome in prostate tissue in rats with experimental autoimmune prostatitis [J]. The Journal of Practical Medicine, 2025, 41(12): 1816-1824.
[7]	Jun LIU,Fulin TIAN,Lin CHEN,Jian. LI. The relationship between normal high blood pressure and grade 1 hypertension in early pregnancy and maternal preeclampsia and adverse pregnancy outcomes [J]. The Journal of Practical Medicine, 2025, 41(10): 1555-1562.
[8]	Fangming WANG,Wenxuan SHANG,Jingwen ZHANG,Yingxiao JI,Litao. LI. Research advances on the regulation of microglia polarization by autophagy in ischemic stroke [J]. The Journal of Practical Medicine, 2024, 40(9): 1324-1330.
[9]	Lulu CHEN,Meng LUO,Kaiqi SU,Jing GAO,Xiaodong. FENG. Research progress of the endoplasmic reticulum⁃mitochondrial interactions in post⁃stroke cognitive impairment [J]. The Journal of Practical Medicine, 2024, 40(7): 1023-1028.
[10]	Ying ZHOU,Dajun JIANG,Yong TIAN,Yongxiang GU,Guohui. YANG. Inhibition of TRAF6 ameliorates myocardial inflammatory injury and cardiac dysfunction via regulating cardiomyocyte inflammation in sepsis mice [J]. The Journal of Practical Medicine, 2024, 40(5): 608-614.
[11]	Zhaohua YAN,Jianbin ZHENG,Na ZHANG,Chunyan CAO,Luchun. YAN. MiR⁃365a⁃3p affects vascular endothelial cell function through TGF⁃β signaling pathway and participates in the pathogenesis of preeclampsia [J]. The Journal of Practical Medicine, 2024, 40(16): 2263-2269.
[12]	Juan LIU,Yanjie LI,Hewei QIN,Luyao MA,Nannan ZHAO,Huimin. DING. Mechanism of action of dysregulated mitochondrial quality control system mediating Parkinson′s disease [J]. The Journal of Practical Medicine, 2024, 40(11): 1479-1482.
[13]	Xue MA,Shihui. ZHOU. Role and potential mechanisms of p62/SQSTM1 on migration and metastasis of non⁃small cell lung cancer [J]. The Journal of Practical Medicine, 2024, 40(1): 13-18.
[14]	Tian GU,Chunhong LIU,Fei ZHANG,Wei QIAN,Yanqiu ZHU,Mingliang CHU,Jiemin. LIU. The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study [J]. The Journal of Practical Medicine, 2024, 40(1): 59-64.
[15]	Tao WU,Suming DING,Chang ZHAN,Wenwen CUI,Weihua. TANG. Changes in serum autophagy markers in infants with retinopathy of prematurity and the clinical value [J]. The Journal of Practical Medicine, 2024, 40(1): 79-84.

Effect of miR⁃15a⁃5p on autophagy of placental trophoblasts in preeclampsia

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 8

References 27

Related Articles 15

Recommended Articles

Metrics

Comments