{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:23:30Z","timestamp":1781835810838,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute lung injury (ALI) is a condition with acute respiratory failure caused by various factors, characterized by severe hypoxemia and diffuse alveolar damage, involving multiple cytokines and signaling pathways. This study investigates the role of secreted phosphoprotein 1 (SPP1) in ALI and explores its underlying mechanisms through a series of in\u00a0vitro and in\u00a0vivo experiments. Our results demonstrate that SPP1 expression is significantly upregulated in ALI animal models, correlating with increased oxidative stress and inflammatory responses. In LPS\u2010induced lung injury models, elevated levels of malondialdehyde (MDA) and IL1\u03b2, along with decreased superoxide dismutase (SOD) levels, were observed, further confirming the active state of SPP1 in ALI. In\u00a0vitro experiments using BEAS\u20102B cells revealed that LPS treatment increased IL1\u03b2 and reactive oxygen species (ROS) levels while decreasing SOD levels, with concomitant upregulation of SPP1. SPP1 knockdown significantly inhibited these changes, directly confirming its regulatory role in ALI progression. We further explored the regulatory mechanisms of SPP1 on the senescence\u2010associated secretory phenotype (SASP), a key pathological process in ALI. SA\u2010\u03b2\u2010GAL staining and \u03b3\u2010H2AX results indicated elevated cellular senescence in LPS\u2010treated cells and ALI models. SPP1 knockdown reduced senescence markers, enhanced cell viability, decreased apoptosis, and improved cell proliferation capacity, suggesting that SPP1 promotes ALI via the SASP phenotype. Mechanistically, we found that SPP1 regulates ALI via the p53 signaling pathway. LPS treatment increased p\u2010p53 levels, whereas SPP1 knockdown reduced p53 activation. The use of a p53 inhibitor further suppressed SASP and improved ALI\u2010related indicators. Animal model validation corroborated these findings, showing that SPP1 knockdown and p53 inhibitor treatment reduced lung tissue damage and improved ALI\u2010related indicators. Collectively, our study reveals a novel mechanism by which SPP1 regulates ALI progression via the p53 signaling pathway and SASP. This discovery not only enriches our understanding of ALI pathogenesis but also provides a new therapeutic target and potential intervention strategies for ALI treatment.<\/jats:p>","DOI":"10.1002\/iub.70038","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T02:20:12Z","timestamp":1751250012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>SPP1<\/scp>\n                    Regulates\n                    <scp>SASP<\/scp>\n                    via the\n                    <scp>p53<\/scp>\n                    Signaling Pathway to Affect\n                    <scp>ALI<\/scp>\n                    Progression"],"prefix":"10.1002","volume":"77","author":[{"given":"Congcong","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyue","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5130-7623","authenticated-orcid":false,"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9081521"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.971189"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04828-7"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-78420-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2041"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04971-x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026070"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","unstructured":"H.Du J. 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