{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:03Z","timestamp":1785413583667,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Fifth People\u2019s Hospital, Fudan University","award":["2024WYRCJY06"],"award-info":[{"award-number":["2024WYRCJY06"]}]},{"award":["2024WYRCJY06"],"award-info":[{"award-number":["2024WYRCJY06"]}],"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}]},{"name":"High-level Professional Physician Training Program of Minhang District","award":["2024MZYS13"],"award-info":[{"award-number":["2024MZYS13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Preeclampsia (PE) is a severe pregnancy-specific hypertensive disorder characterized by immune microenvironment dysregulation at the maternal\u2013fetal interface, with decidual macrophage phenotypic imbalance being a key pathological feature. The Ghrelin\/growth hormone secretagogue receptor-1a (GHSR-1a) axis exerts immunomodulatory and anti-inflammatory effects, but its role in regulating decidual macrophage infiltration and phenotypic marker expression in PE remains unclear. In this study, we first detected the expression of the Ghrelin\/GHSR-1a axis in decidual tissues from 10 healthy pregnant women and 12 PE patients via immunohistochemistry (IHC). We then established a lipopolysaccharide (LPS)-induced PE-like rat model to investigate the axis\u2019s functional role and underlying mechanisms. Intriguingly, clinical analysis revealed a severity-dependent compensatory escalation of the Ghrelin\/GHSR-1a axis in PE decidual tissues, potentially representing an endogenous antagonistic response to pregnancy-associated pathological stress. In the animal model, exogenous Ghrelin supplementation reversed LPS-induced PE-like phenotypes, including hypertension, proteinuria, fetal growth restriction (FGR), and placental dysfunction, and alleviated pathological damage to the maternal liver, kidney, and placenta. Mechanistically, Ghrelin modulated decidual macrophage phenotypic marker expression by downregulating the M1 marker CD86 and upregulating the M2 marker CD163 and promoted trophoblast invasion and spiral artery remodeling by restoring laminin, \u03b1-cytokeratin 7 (\u03b1-CK7), and \u03b1-smooth muscle actin (\u03b1-SMA) expression in placental tissue. All protective effects of Ghrelin were abrogated by co-administration of D-lys-3-GHRP-6, a specific GHSR-1a antagonist, confirming the dependence on the Ghrelin\/GHSR-1a axis. Collectively, our findings suggest that the Ghrelin\/GHSR-1a axis is compensatorily upregulated in PE and may exert a protective role by regulating decidual macrophage phenotypic marker expression and improving placental function, providing preliminary evidence that this axis merits further investigation as a potential research target for PE.<\/jats:p>","DOI":"10.3390\/biom16060809","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:08:02Z","timestamp":1780535282000},"page":"809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Ghrelin\/GHSR-1a Axis Attenuates Preeclampsia-like Features with Decidual Macrophage Reprogramming and Improved Placental Remodeling"],"prefix":"10.3390","volume":"16","author":[{"given":"Lingling","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Center of Community-Based Health Research, Fudan University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Center of Community-Based Health Research, Fudan University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Center of Community-Based Health Research, Fudan University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yu","sequence":"additional","affiliation":[{"name":"Center of Community-Based Health Research, Fudan University, Shanghai 200240, China"},{"name":"Department of Central Laboratory, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Center of Community-Based Health Research, Fudan University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-6280","authenticated-orcid":false,"given":"Rujun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Center of Community-Based Health Research, Fudan University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Center of Community-Based Health Research, Fudan University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41572-023-00417-6","article-title":"Pre-eclampsia","volume":"9","author":"Dimitriadis","year":"2023","journal-title":"Nat. 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