{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:38:42Z","timestamp":1771922322390,"version":"3.50.1"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R21HD110797"],"award-info":[{"award-number":["R21HD110797"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Placental inflammation is a major contributor to preterm birth (PTB), and there are currently few targeted strategies to prevent PTB and its associated adverse neonatal outcomes. Serum amyloid A (SAA), particularly the isoforms SAA1 and SAA2, are well-recognized inflammatory markers, but their functional roles in placental inflammation remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using a translational mouse model of sub-chronic maternal inflammation, we investigated the immune mechanisms and therapeutic potential of siRNA-mediated targeting of Saa2 (siSaa2). Placental expression patterns of SAA2 were examined\n                      <jats:italic>in vivo<\/jats:italic>\n                      , and macrophage responses to extracellular SAA2 were modeled in vitro using RAW264.7 cells to assess downstream P2X7R-dependent signaling and functional outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SAA2 is primarily induced in placental trophoblast and endothelial compartments during inflammation, where it acts as an extracellular inflammatory mediator.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , we model macrophage responses to extracellular SAA2 using RAW264.7 cells to examine downstream P2X7R-dependent signaling and functional outcomes. Maternal administration of siSaa2 improved PTB rates, placental morphology and fetal brain development. Additionally, SAA1 and SAA2 exhibited distinct expression patterns in the mouse and human placenta.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify placental SAA2 as a key inflammatory mediator in inflammation-associated PTB and demonstrate that targeted silencing of Saa2 represents a potential therapeutic strategy to mitigate placental injury and adverse fetal outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1749966","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:21:26Z","timestamp":1768540886000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting SAA expression via siRNA mitigates preterm birth induced by maternal inflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jun","family":"Lei","sequence":"first","affiliation":[{"name":"Integrated Research Center for Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrated Research Center for Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrated Research Center for Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Jones-Beatty","sequence":"additional","affiliation":[{"name":"Integrated Research Center for Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth Ann L.","family":"Enninga","sequence":"additional","affiliation":[{"name":"Maternal Fetal Medicine Division, Department of Obstetrics and Gynecology, Mayo Clinic","place":["Rochester, MN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney","family":"Townsel","sequence":"additional","affiliation":[{"name":"Integrated Research Center for Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Burd","sequence":"additional","affiliation":[{"name":"Integrated Research Center for Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine","place":["Baltimore, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5535","DOI":"10.1242\/jcs.111260","article-title":"Macrophages require Skap2 and Sirpalpha for integrin-stimulated cytoskeletal rearrangement","volume":"125","author":"Alenghat","year":"2012","journal-title":"J. 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