Abstract
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-α and IL-1β), and anti-inflammatory cytokines (IL-10 and TGF-β) 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. HucMSC-Exo 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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The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
Aggarwal R et al (2019) Association of pro- and anti-inflammatory cytokines in preeclampsia. J Clin Lab Anal 33(4):e22834
Bitaraf A, Babashah S, Garshasbi M (2020) Aberrant expression of a five-microRNA signature in breast carcinoma as a promising biomarker for diagnosis. J Clin Lab Anal 34(2):e23063
Chaiwangyen W et al (2015) Dissimilar microRNA-21 functions and targets in trophoblastic cell lines of different origin. Int J Biochem Cell Biol 68:187–196
Chaiwangyen W et al (2020) MiR-519d-3p in trophoblastic cells: effects, targets and transfer to allogeneic immune cells via extracellular vesicles. Int J Mol Sci 21(10)
Chen CY et al (2015) Human placenta-derived multipotent mesenchymal stromal cells involved in placental angiogenesis via the PDGF-BB and STAT3 pathways. Biol Reprod 93(4):103
Ding L et al (2016) Higher PDCD4 expression is associated with obesity, insulin resistance, lipid metabolism disorders, and granulosa cell apoptosis in polycystic ovary syndrome. Fertil Steril 105(5):1330-1337 e3
Du T et al (2020) Microvesicles derived from human umbilical cord mesenchymal stem cells ameliorate renal ischemia-reperfusion injury via delivery of miR-21. Cell Cycle 19(11):1285–1297
Eastabrook G et al (2018) Preeclampsia biomarkers: an assessment of maternal cardiometabolic health. Pregnancy Hypertens 13:204–213
Flint EJ et al (2019) The role of angiogenic factors in the management of preeclampsia. Acta Obstet Gynecol Scand 98(6):700–707
Fu X et al (2017) Overexpression of miR-21 in stem cells improves ovarian structure and function in rats with chemotherapy-induced ovarian damage by targeting PDCD4 and PTEN to inhibit granulosa cell apoptosis. Stem Cell Res Ther 8(1):187
Fu X et al (2018) MicroRNA-16 promotes ovarian granulosa cell proliferation and suppresses apoptosis through targeting PDCD4 in polycystic ovarian syndrome. Cell Physiol Biochem 48(2):670–682
Han X et al (2020) MiR-342-3p inhibition promotes cell proliferation and invasion by directly targeting ID4 in pre-eclampsia. J Obstet Gynaecol Res 46(1):49–57
Hu S et al (2019) MicroRNA1443p may participate in the pathogenesis of preeclampsia by targeting Cox2. Mol Med Rep 19(6):4655–4662
Hu Y et al (2020) Human umbilical cord mesenchymal stromal cells-derived extracellular vesicles exert potent bone protective effects by CLEC11A-mediated regulation of bone metabolism. Theranostics 10(5):2293–2308
Huang Q et al (2021) Human umbilical cord mesenchymal stem cells-derived exosomal MicroRNA-18b-3p inhibits the occurrence of preeclampsia by targeting LEP. Nanoscale Res Lett 16(1):27
Li Y et al (2017) The expression of PDCD4 in patients with missed abortion and its clinical significance. Reprod Sci 24(11):1512–1519
Li S et al (2018) Cardiac progenitor cell-derived exosomes promote H9C2 cell growth via Akt/mTOR activation. Int J Mol Med 42(3):1517–1525
Li X et al (2019a) Human umbilical cord mesenchymal stem cell-derived extracellular vesicles inhibit endometrial cancer cell proliferation and migration through delivery of exogenous miR-302a. Stem Cells Int 2019:8108576
Li Y et al (2019b) Exosomal miR-301 derived from mesenchymal stem cells protects myocardial infarction by inhibiting myocardial autophagy. Biochem Biophys Res Commun 514(1):323–328
Liu Y et al (2019) Adipose-derived exosomes deliver miR-23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis. J Physiol Biochem 75(3):391–401
Malik A, Jee B, Gupta SK (2019) Preeclampsia: disease biology and burden, its management strategies with reference to India. Pregnancy Hypertens 15:23–31
Nong K et al (2016) Hepatoprotective effect of exosomes from human-induced pluripotent stem cell-derived mesenchymal stromal cells against hepatic ischemia-reperfusion injury in rats. Cytotherapy 18(12):1548–1559
Rana S et al (2019) Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res 124(7):1094–1112
Ray SL et al (2020) The role of miR-342 in vascular health. study in subclinical cardiovascular disease in mononuclear cells, plasma, inflammatory cytokines and PANX2. Int J Mol Sci 21(19)
Sun W et al (2017) Neuroprotective potential of gentongping in rat model of cervical spondylotic radiculopathy targeting PPAR-gamma pathway. J Immunol Res 2017:9152960
Sun G et al (2018) hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation. Mater Sci Eng C Mater Biol Appl 89:194–204
Tuo YL, Li XM, Luo J (2015) Long noncoding RNA UCA1 modulates breast cancer cell growth and apoptosis through decreasing tumor suppressive miR-143. Eur Rev Med Pharmacol Sci 19(18):3403–3411
Wang Z et al (2019) MiRNA-548c-5p downregulates inflammatory response in preeclampsia via targeting PTPRO. J Cell Physiol 234(7):11149–11155
Xiao S et al (2018) Celastrol attenuates symptoms of preeclampsia in rats by inhibiting matrix metalloproteinase-9. Eur J Pharmacol 830:33–38
Xiong ZH et al (2018) Protective effect of human umbilical cord mesenchymal stem cell exosomes on preserving the morphology and angiogenesis of placenta in rats with preeclampsia. Biomed Pharmacother 105:1240–1247
Yaghoubi Y et al (2019) Human umbilical cord mesenchymal stem cells-derived exosomes in diseases treatment. Life Sci 233:116733
Yan T et al (2014) Assessment of therapeutic efficacy of miR-126 with contrast-enhanced ultrasound in preeclampsia rats. Placenta 35(1):23–29
Yang X, Guo F (2019) miR3423p suppresses cell migration and invasion in preeclampsia by targeting plateletderived growth factor receptor alpha. Mol Med Rep 20(2):1772–1780
Yang R et al (2018) Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter. Nat Commun 9(1):2143
Yang BC et al (2020) Human umbilical cord mesenchymal stem cell-derived exosomes act via the miR-1263/Mob1/Hippo signaling pathway to prevent apoptosis in disuse osteoporosis. Biochem Biophys Res Commun 524(4):883–889
You J et al (2019) Snail1-dependent cancer-associated fibroblasts induce epithelial-mesenchymal transition in lung cancer cells via exosomes. QJM 112(8):581–590
Zhang Y et al (2018) Expression and function of Pdcd4 in mouse endometrium during early pregnancy. Reproduction 155(4):393–402
Zhang R et al (2020) Human umbilical cord mesenchymal stem cell exosomes alleviate sepsis-associated acute kidney injury via regulating microRNA-146b expression. Biotechnol Lett 42(4):669–679
Zhao Y et al (2018) Inhibiting trophoblast PAR-1 overexpression suppresses sFlt-1-induced anti-angiogenesis and abnormal vascular remodeling: a possible therapeutic approach for preeclampsia. Mol Hum Reprod 24(3):158–169
Zhao L et al (2020) miR-33-5p knockdown attenuates abdominal aortic aneurysm progression via promoting target adenosine triphosphate-binding cassette transporter A1 expression and activating the PI3K/Akt signaling pathway. Perfusion 35(1):57–65
Zhu J et al (2015) Transplantation of endothelial progenitor cells for improving placental perfusion in preeclamptic rats. Arch Gynecol Obstet 291(5):1113–1119
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This work was supported by the study on the correlation between early spontaneous abortion and villus chromosome abnormality [grant number 2014C312068].
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Hb.R. contributed to study design; Y.C. contributed to manuscript editing; Jx.J. and Xp.C. contributed to experimental studies; J.X. and Lh.A. contributed to data analysis.
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Written informed consent was acquired from all patients before this study. Animal experiments were accorded with the Guide to the Management and Use of Laboratory Animals issued by the National Institutes of Health. The protocol of this study was approved by the Ethics Committee of the First People’s Hospital of WenLing ZheJiang and based on the ethical principles of the Helsinki Declaration. The protocol of animal experiments was approved by the Institutional Animal Care and Use Committee of the First People’s Hospital of WenLing ZheJiang.
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Chen, Y., Jin, J., Chen, X. et al. Exosomal microRNA-342-5p from human umbilical cord mesenchymal stem cells inhibits preeclampsia in rats. Funct Integr Genomics 23, 27 (2023). https://doi.org/10.1007/s10142-022-00931-y
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DOI: https://doi.org/10.1007/s10142-022-00931-y