Exosomal microRNA-342-5p from human umbilical cord mesenchymal stem cells inhibits preeclampsia in rats

被引:14
作者
Chen, Yi [1 ]
Jin, Jiaxi [1 ]
Chen, XiaoPei [1 ]
Xu, Jia [1 ]
An, Lihong [1 ]
Ruan, Haibo [1 ]
机构
[1] First Peoples Hosp WenLing ZheJiang, Dept Obstet & Gynecol, 333 Chuanannan Rd,Chengxi St, Wenling 317500, Zhejiang, Peoples R China
关键词
Preeclampsia; Mesenchymal stem cell-derived exosome; MicroRNA-342-5p; Programmed cell death 4; STROMAL CELLS; APOPTOSIS; PDCD4; EXPRESSION; ANGIOGENESIS; INJURY;
D O I
10.1007/s10142-022-00931-y
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We aimed to investigate the inhibitory effect of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes (hucMSC-Exos) transmitting microRNA-342-5p (miR-342-5p) on the development of preeclampsia (PE) by targeting programmed cell death 4 (PDCD4). The primary hucMSCs were cultured and transfected with miR-342-5p, and the exosomes (Exo) were extracted from the hucMSCs. PE rats were performed with an intraperitoneal injection of L-NAME from days 11 to 19 of gestation, and injection of Exo, Exo-negative control (NC), Exo-miR-342-5p agomir, Exo-miR-342-5p antagomir, and overexpressing PDCD4 (oe-PDCD4) vector into the placenta on the 16th day of pregnancy. HE staining was utilized to observe the pathological changes in placental tissues. TUNEL staining was implemented to evaluate cell apoptosis in placental tissues. Blood pressure and 24-h urinary protein in pregnant rats were measured by a non-invasive rat tail artery blood pressure measurement and protein auto-analyzer. Expressions of miR-342-5p, PDCD4, proinflammatory cytokines (TNF-alpha and IL-1 beta), and anti-inflammatory cytokines (IL-10 and TGF-beta) were detected by RT-qPCR, and PDCD4 protein expression was determined by Western blot. The interaction between miR-342-5p and PDCD4 was analyzed by luciferase activity assay. MiR-342-5p was downregulated while PDCD4 was upregulated in the placental tissues of PE rats. HucMSCExo relieved pathology and suppressed inflammatory response, and apoptosis in the placental tissues, as well as reducing blood pressure and 24-h urinary protein of PE rats. Elevated miR-342-5p enhanced the promoting influence of hucMSC-Exo on PE rats, while inhibited miR-342-5p reversed the functions of hucMSC-Exo on PE rats. miR-342-5p targeted PDCD4. Overexpression of PDCD4 worsened the development of PE in rats. HucMSC-Exo conveying elevated miR-342-5p inhibits the development of PE in a rat model through downregulating PDCD4.
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页数:11
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共 41 条
[1]   Association of pro- and anti-inflammatory cytokines in preeclampsia [J].
Aggarwal, Ruby ;
Jain, Arun Kumar ;
Mittal, Pratima ;
Kohli, Mangala ;
Jawanjal, Poonam ;
Rath, Gayatri .
JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2019, 33 (04)
[2]   Aberrant expression of a five-microRNA signature in breast carcinoma as a promising biomarker for diagnosis [J].
Bitaraf, Amirreza ;
Babashah, Sadegh ;
Garshasbi, Masoud .
JOURNAL OF CLINICAL LABORATORY ANALYSIS, 2020, 34 (02)
[3]   MiR-519d-3p in Trophoblastic Cells: Effects, Targets and Transfer to Allogeneic Immune Cells via Extracellular Vesicles [J].
Chaiwangyen, Wittaya ;
Murrieta-Coxca, Jose M. ;
Favaro, Rodolfo R. ;
Photini, Stella M. ;
Gutierrez-Samudio, Ruby N. ;
Schleussner, Ekkehard ;
Markert, Udo R. ;
Morales-Prieto, Diana M. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (10)
[4]   Dissimilar microRNA-21 functions and targets in trophoblastic cell lines of different origin [J].
Chaiwangyen, Wittaya ;
Ospina-Prieto, Stephanie ;
Photini, Stella Mary ;
Schleussner, Ekkehard ;
Markert, Udo R. ;
Morales-Prieto, Diana M. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2015, 68 :187-196
[5]   Human Placenta-Derived Multipotent Mesenchymal Stromal Cells Involved in Placental Angiogenesis via the PDGF-BB and STAT3 Pathways [J].
Chen, Cheng-Yi ;
Liu, Shu-Hsiang ;
Chen, Chia-Yu ;
Chen, Pei-Chun ;
Chen, Chie-Pein .
BIOLOGY OF REPRODUCTION, 2015, 93 (04)
[6]   Higher PDCD4 expression is associated with obesity, insulin resistance, lipid metabolism disorders, and granulosa cell apoptosis in polycystic ovary syndrome [J].
Ding, Lingling ;
Gao, Fei ;
Zhang, Meng ;
Yan, Wenjiang ;
Tang, Rong ;
Zhang, Cheng ;
Chen, Zi-Jiang .
FERTILITY AND STERILITY, 2016, 105 (05) :1330-+
[7]   Microvesicles derived from human umbilical cord mesenchymal stem cells ameliorate renal ischemia-reperfusion injury via delivery of miR-21 [J].
Du, Tao ;
Zhou, Jun ;
Chen, Wen-Xia ;
Zhang, Xiao-Li ;
Ji, Tong-Yu ;
Liu, Jie ;
Rong, Lu ;
Wang, Ling-Dian ;
Zhou, Rui-Jin ;
Ding, De-Gang .
CELL CYCLE, 2020, 19 (11) :1285-1297
[8]   Preeclampsia biomarkers: An assessment of maternal cardiometabolic health [J].
Eastabrook, Genevieve ;
Aksoy, Tuba ;
Bedell, Samantha ;
Penava, Debbie ;
de Vrijer, Barbra .
PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH, 2018, 13 :204-213
[9]   The role of angiogenic factors in the management of preeclampsia [J].
Flint, Emma J. ;
Cerdeira, A. Sofia ;
Redman, Christopher W. ;
Vatish, Manu .
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 2019, 98 (06) :700-707
[10]   MicroRNA-16 Promotes Ovarian Granulosa Cell Proliferation and Suppresses Apoptosis Through Targeting PDCD4 in Polycystic Ovarian Syndrome [J].
Fu, Xiafei ;
He, Yuanli ;
Wang, Xuefeng ;
Peng, Dongxian ;
Chen, Xiaoying ;
Li, Xinran ;
Wan, Qing .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 48 (02) :670-682