Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation
The placental inflammatory processes induced maternally result in preterm birth (PTB). Serum amyloid A (SAA) is a well-known biomarker of inflammation. The objective of this study was to investigate whether murine placental SAA isoforms (SAA1–4) participate in the mechanism of spontaneous PTB and wh...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.902096/full |
| _version_ | 1828235534091157504 |
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| author | Yang Liu Yang Liu Jin Liu Anguo Liu Hillary Yin Irina Burd Jun Lei |
| author_facet | Yang Liu Yang Liu Jin Liu Anguo Liu Hillary Yin Irina Burd Jun Lei |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | The placental inflammatory processes induced maternally result in preterm birth (PTB). Serum amyloid A (SAA) is a well-known biomarker of inflammation. The objective of this study was to investigate whether murine placental SAA isoforms (SAA1–4) participate in the mechanism of spontaneous PTB and whether maternal regulation of SAA production may serve as a therapeutic approach. During the gestation, all isoforms of SAA were detectable except SAA2. The mouse model of intrauterine inflammation was established using LPS infusion to the uterus. Following intrauterine inflammation, placental SAA2 increased significantly. Inhibition of Saa2, using siSaa2, markedly decreased PTB. The increased placental expression of pro-inflammatory cytokines Il1β, Il6, and Tnfα were downregulated by siSaa2 treatment. Maternal inhibition of Saa2 did not change the expression of Saa1–4 in the fetal brain. Explant inflammatory culture of placentas with siSaa2 showed similar results to our in vivo experiments. This study demonstrates the highly expressed placental SAA2 as a novel therapeutic target, and maternal administration of siRNA as a promising approach to alleviate PTB. |
| first_indexed | 2024-04-12T20:16:50Z |
| format | Article |
| id | doaj.art-286652d296bc406f8859a5213f33dbf4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T20:16:50Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-286652d296bc406f8859a5213f33dbf42022-12-22T03:18:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.902096902096Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammationYang Liu0Yang Liu1Jin Liu2Anguo Liu3Hillary Yin4Irina Burd5Jun Lei6Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, ChinaIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesIntegrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesThe placental inflammatory processes induced maternally result in preterm birth (PTB). Serum amyloid A (SAA) is a well-known biomarker of inflammation. The objective of this study was to investigate whether murine placental SAA isoforms (SAA1–4) participate in the mechanism of spontaneous PTB and whether maternal regulation of SAA production may serve as a therapeutic approach. During the gestation, all isoforms of SAA were detectable except SAA2. The mouse model of intrauterine inflammation was established using LPS infusion to the uterus. Following intrauterine inflammation, placental SAA2 increased significantly. Inhibition of Saa2, using siSaa2, markedly decreased PTB. The increased placental expression of pro-inflammatory cytokines Il1β, Il6, and Tnfα were downregulated by siSaa2 treatment. Maternal inhibition of Saa2 did not change the expression of Saa1–4 in the fetal brain. Explant inflammatory culture of placentas with siSaa2 showed similar results to our in vivo experiments. This study demonstrates the highly expressed placental SAA2 as a novel therapeutic target, and maternal administration of siRNA as a promising approach to alleviate PTB.https://www.frontiersin.org/articles/10.3389/fimmu.2022.902096/fullpreterm birthintrauterine inflammationserum amyloid A (SAA)placentasiRNA treatment |
| spellingShingle | Yang Liu Yang Liu Jin Liu Anguo Liu Hillary Yin Irina Burd Jun Lei Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation Frontiers in Immunology preterm birth intrauterine inflammation serum amyloid A (SAA) placenta siRNA treatment |
| title | Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation |
| title_full | Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation |
| title_fullStr | Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation |
| title_full_unstemmed | Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation |
| title_short | Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation |
| title_sort | maternal sirna silencing of placental saa2 mitigates preterm birth following intrauterine inflammation |
| topic | preterm birth intrauterine inflammation serum amyloid A (SAA) placenta siRNA treatment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.902096/full |
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