{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:52:25Z","timestamp":1791280345444,"version":"4.1.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ventilator-induced lung injury (VILI) is a major iatrogenic complication of mechanical ventilation, in which dysregulated inflammation, particularly macrophage-driven response, amplifies pulmonary damage. Although bone morphogenetic protein (BMP) signaling exhibits context-dependent effects in pulmonary disorders, whether specific BMP receptors (BMPRs) regulate macrophage function during VILI remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice subjected to mechanical ventilation were randomly divided into Control (intubation without ventilation), LVT (low tidal volume), and HVT (high tidal volume) groups. HVT-exposed mice received intratracheal administration of exogenous BMP4 or the BMP type I receptor antagonist LDN193189.  Lung injury severity was assessed by ultrasound, macroscopic scoring, wet\/dry ratio, and histopathology. Macrophage accumulation, M1\/M2 polarization, interstitial-to-alveolar macrophage (IM\/AM) ratio, and BMP receptor expression were evaluated. Transcriptomic profiling was performed to identify differentially expressed genes and enriched pathways. In vitro, gain- and loss-of-function experiments (overexpression and knockdown of BMPRIB) were conducted in RAW264.7 macrophages to assess cytokine\/chemokine production, migration, and MAPK pathway activation. The p38 inhibitor SB202190 was used to probe downstream signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with Control and LVT groups, HVT induced time-dependent macrophage accumulation, skewed M1\/M2 polarization, and a progressive elevation of the IM\/AM ratio. Strikingly, HVT selectively upregulated BMPRIB in lung macrophages, while downregulating BMPRII and leaving BMPRIA unchanged. Intratracheal BMP4 exacerbated these effects, whereas LDN193189 reversed BMP4-induced macrophage accumulation, M1 polarization, IM\/AM elevation, and suppressed activation of ERK, JNK, p38, and p65 signaling. Transcriptomic analysis revealed that BMP4 enriched MAPK and inflammation-related pathways, with LDN193189 co-treatment partially reversing this enrichment. In BMP4-stimulated RAW264.7 macrophages, BMPRIB overexpression enhanced, whereas BMPRIB knockdown attenuated, cytokine\/chemokine production and migration. Pharmacological p38 inhibition (SB202190) abrogated BMP4-induced pro-inflammatory effects in macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HVT-induced BMPRIB upregulation in lung macrophages allows BMP4 to activate BMPRIB-dependent p38\/NF-\u03baB p65 axis as a key mediator of macrophage-driven inflammation in VILI Targeting the BMPRIB-dependent p38\/NF-\u03baB axis may represent a novel therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1947415","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:03:52Z","timestamp":1791277432000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage BMPRIB mediates p38-dependent inflammatory reprogramming and chemotaxis during ventilator-induced lung injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]},{"name":"Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]},{"name":"Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]},{"name":"Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]},{"name":"Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Xiangya Hospital, Central South University","place":["Changsha, Hunan, China"]},{"name":"Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.13374","article-title":"Effect of lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal vs standard care ventilation on 90-day mortality in patients with acute hypoxemic respiratory failure: The REST randomized clinical trial","volume":"326","author":"McNamee","year":"2021","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262110448","article-title":"Ventilator-associated lung injury: Pathophysiology, prevention, and emerging therapeutic strategies","volume":"26","author":"Costa","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201907-1283CI","article-title":"Mechanical ventilation for acute respiratory distress syndrome during extracorporeal life support. 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