{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:41:48Z","timestamp":1793324508314,"version":"4.5.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the Basic Research Project of Yunnan Provincial Science and Technology Department","award":["202401AY070001-020"],"award-info":[{"award-number":["202401AY070001-020"]}]},{"name":"Beijing Natural Science Foundation","award":["7232077"],"award-info":[{"award-number":["7232077"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82300301"],"award-info":[{"award-number":["82300301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-34794-7","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:54:26Z","timestamp":1767894866000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Piezo1 knockdown activates PI3K\/AKT and enhances SPP1 to drive M2 macrophage polarization and reduce cardiac inflammation"],"prefix":"10.1038","volume":"16","author":[{"given":"Yunhan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoyan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuzhe","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinbo","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangwei","family":"Nong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boheng","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyuan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiling","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjiang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donglin","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiu","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"34794_CR1","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41569-020-00492-2","volume":"18","author":"SM Hollenberg","year":"2021","unstructured":"Hollenberg, S. M. & Singer, M. Pathophysiology of sepsis-induced cardiomyopathy. Nat. Rev. Cardiol. 18, 424\u2013434. https:\/\/doi.org\/10.1038\/s41569-020-00492-2 (2021).","journal-title":"Nat. Rev. Cardiol."},{"key":"34794_CR2","doi-asserted-by":"publisher","first-page":"3256","DOI":"10.1038\/s41467-021-23482-5","volume":"12","author":"H Atcha","year":"2021","unstructured":"Atcha, H. et al. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat. Commun. 12, 3256. https:\/\/doi.org\/10.1038\/s41467-021-23482-5 (2021).","journal-title":"Nat. Commun."},{"key":"34794_CR3","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1002\/biof.1681","volume":"46","author":"W Liang","year":"2020","unstructured":"Liang, W. et al. Interleukin-5 deletion promotes sepsis-induced M1 macrophage differentiation, deteriorates cardiac dysfunction, and exacerbates cardiac injury via the NF-\u03baB p65 pathway in mice. BioFactors 46, 1006\u20131017. https:\/\/doi.org\/10.1002\/biof.1681 (2020).","journal-title":"BioFactors"},{"key":"34794_CR4","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.632912","volume":"12","author":"Z Wang","year":"2021","unstructured":"Wang, Z. et al. Il12a deletion aggravates sepsis-induced cardiac dysfunction by regulating macrophage polarization. Front. Pharmacol. 12, 632912. https:\/\/doi.org\/10.3389\/fphar.2021.632912 (2021).","journal-title":"Front. Pharmacol."},{"key":"34794_CR5","doi-asserted-by":"publisher","first-page":"17253","DOI":"10.1073\/pnas.1308887110","volume":"110","author":"FY McWhorter","year":"2013","unstructured":"McWhorter, F. Y., Wang, T., Nguyen, P., Chung, T. & Liu, W. F. Modulation of macrophage phenotype by cell shape. Proc. Natl. Acad. Sci. U S A 110, 17253\u201317258. https:\/\/doi.org\/10.1073\/pnas.1308887110 (2013).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"34794_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119467","volume":"277","author":"D Li","year":"2021","unstructured":"Li, D. et al. Maresin 1 alleviates the inflammatory response, reduces oxidative stress and protects against cardiac injury in LPS-induced mice. Life Sci. 277, 119467. https:\/\/doi.org\/10.1016\/j.lfs.2021.119467 (2021).","journal-title":"Life Sci."},{"issue":"Suppl N","key":"34794_CR7","first-page":"N25","volume":"19","author":"AH Wu","year":"1998","unstructured":"Wu, A. H. & Feng, Y. J. Biochemical differences between cTnT and cTnI and their significance for diagnosis of acute coronary syndromes. Eur. Heart J. 19(Suppl N), N25-29 (1998).","journal-title":"Eur. Heart J."},{"key":"34794_CR8","doi-asserted-by":"publisher","first-page":"3519","DOI":"10.1038\/s41467-021-23683-y","volume":"12","author":"J Geng","year":"2021","unstructured":"Geng, J. et al. TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection. Nat. Commun. 12, 3519. https:\/\/doi.org\/10.1038\/s41467-021-23683-y (2021).","journal-title":"Nat. Commun."},{"key":"34794_CR9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.7150\/thno.36930","volume":"10","author":"SJ Zhao","year":"2020","unstructured":"Zhao, S. J. et al. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K\/AKT\/GSK3\u03b2\/\u03b2-catenin pathway. Theranostics 10, 17\u201335. https:\/\/doi.org\/10.7150\/thno.36930 (2020).","journal-title":"Theranostics"},{"key":"34794_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41586-019-1485-8","volume":"573","author":"AG Solis","year":"2019","unstructured":"Solis, A. G. et al. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 573, 69\u201374. https:\/\/doi.org\/10.1038\/s41586-019-1485-8 (2019).","journal-title":"Nature"},{"key":"34794_CR11","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1161\/circulationaha.120.045536","volume":"142","author":"S Baratchi","year":"2020","unstructured":"Baratchi, S. et al. Transcatheter aortic valve implantation represents an anti-inflammatory therapy via reduction of shear stress-induced, piezo-1-mediated monocyte activation. Circulation 142, 1092\u20131105. https:\/\/doi.org\/10.1161\/circulationaha.120.045536 (2020).","journal-title":"Circulation"},{"key":"34794_CR12","doi-asserted-by":"publisher","first-page":"eaab5168","DOI":"10.1126\/sciimmunol.abb5168","volume":"5","author":"B Aykut","year":"2020","unstructured":"Aykut, B. et al. Targeting Piezo1 unleashes innate immunity against cancer and infectious disease. Sci. Immunol. 5, eaab5168. https:\/\/doi.org\/10.1126\/sciimmunol.abb5168 (2020).","journal-title":"Sci. Immunol."},{"key":"34794_CR13","doi-asserted-by":"publisher","first-page":"6425","DOI":"10.1002\/jcp.26429","volume":"233","author":"A Shapouri-Moghaddam","year":"2018","unstructured":"Shapouri-Moghaddam, A. et al. Macrophage plasticity, polarization, and function in health and disease. J. Cell Physiol. 233, 6425\u20136440. https:\/\/doi.org\/10.1002\/jcp.26429 (2018).","journal-title":"J. Cell Physiol."},{"key":"34794_CR14","doi-asserted-by":"publisher","first-page":"5418","DOI":"10.7150\/thno.86103","volume":"13","author":"S Luo","year":"2023","unstructured":"Luo, S. et al. Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice. Theranostics 13, 5418\u20135434. https:\/\/doi.org\/10.7150\/thno.86103 (2023).","journal-title":"Theranostics"},{"key":"34794_CR15","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.yexcr.2017.08.028","volume":"359","author":"Y Zhang","year":"2017","unstructured":"Zhang, Y., Du, W., Chen, Z. & Xiang, C. Upregulation of PD-L1 by SPP1 mediates macrophage polarization and facilitates immune escape in lung adenocarcinoma. Exp. Cell Res. 359, 449\u2013457. https:\/\/doi.org\/10.1016\/j.yexcr.2017.08.028 (2017).","journal-title":"Exp. Cell Res."},{"key":"34794_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.739358","volume":"9","author":"B Dong","year":"2021","unstructured":"Dong, B., Wu, C., Huang, L. & Qi, Y. Macrophage-related SPP1 as a potential biomarker for early lymph node metastasis in lung adenocarcinoma. Front. Cell Dev. Biol. 9, 739358. https:\/\/doi.org\/10.3389\/fcell.2021.739358 (2021).","journal-title":"Front. Cell Dev. Biol."},{"key":"34794_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108724","volume":"34","author":"Q Yuan","year":"2021","unstructured":"Yuan, Q. et al. MyD88 in myofibroblasts enhances colitis-associated tumorigenesis via promoting macrophage M2 polarization. Cell Rep. 34, 108724. https:\/\/doi.org\/10.1016\/j.celrep.2021.108724 (2021).","journal-title":"Cell Rep."},{"key":"34794_CR18","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkae909","volume":"53","author":"M Kanehisa","year":"2025","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: Biological systems database as a model of the real world. Nucleic Acids Res. 53, D672-d677. https:\/\/doi.org\/10.1093\/nar\/gkae909 (2025).","journal-title":"Nucleic Acids Res."},{"key":"34794_CR19","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","volume":"44","author":"M Kanehisa","year":"2016","unstructured":"Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M. & Tanabe, M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44, D457-462. https:\/\/doi.org\/10.1093\/nar\/gkv1070 (2016).","journal-title":"Nucleic Acids Res."},{"key":"34794_CR20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa, M. & Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27\u201330. https:\/\/doi.org\/10.1093\/nar\/28.1.27 (2000).","journal-title":"Nucleic Acids Res."},{"key":"34794_CR21","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1161\/hypertensionaha.121.18750","volume":"79","author":"Y He","year":"2022","unstructured":"He, Y. et al. Myeloid Piezo1 deletion protects renal fibrosis by restraining macrophage infiltration and activation. Hypertension 79, 918\u2013931. https:\/\/doi.org\/10.1161\/hypertensionaha.121.18750 (2022).","journal-title":"Hypertension"},{"key":"34794_CR22","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200314R","volume":"36","author":"H Xu","year":"2022","unstructured":"Xu, H. et al. Mechanical force modulates macrophage proliferation via Piezo1-AKT-Cyclin D1 axis. Faseb J. 36, e22423. https:\/\/doi.org\/10.1096\/fj.202200314R (2022).","journal-title":"Faseb J."},{"key":"34794_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116050","volume":"222","author":"H Liu","year":"2024","unstructured":"Liu, H. et al. Dexamethasone upregulates macrophage PIEZO1 via SGK1, suppressing inflammation and increasing ROS and apoptosis. Biochem. Pharmacol. 222, 116050. https:\/\/doi.org\/10.1016\/j.bcp.2024.116050 (2024).","journal-title":"Biochem. Pharmacol."},{"key":"34794_CR24","doi-asserted-by":"publisher","first-page":"1499858","DOI":"10.3389\/fimmu.2025.1499858","volume":"16","author":"SMN Rahman","year":"2025","unstructured":"Rahman, S. M. N., Yung, J. H. M., Volchuk, A., Goldenberg, N. M. & Giacca, A. Metabolic phenotypes in a Lyz2Cre recombinase mouse model. Front. Immunol. 16, 1499858. https:\/\/doi.org\/10.3389\/fimmu.2025.1499858 (2025).","journal-title":"Front. Immunol."},{"key":"34794_CR25","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nature12034","volume":"496","author":"TA Wynn","year":"2013","unstructured":"Wynn, T. A., Chawla, A. & Pollard, J. W. Macrophage biology in development, homeostasis and disease. Nature 496, 445\u2013455. https:\/\/doi.org\/10.1038\/nature12034 (2013).","journal-title":"Nature"},{"key":"34794_CR26","doi-asserted-by":"publisher","first-page":"792","DOI":"10.3389\/fimmu.2019.00792","volume":"10","author":"Y Yao","year":"2019","unstructured":"Yao, Y., Xu, X. H. & Jin, L. Macrophage polarization in physiological and pathological pregnancy. Front. Immunol. 10, 792. https:\/\/doi.org\/10.3389\/fimmu.2019.00792 (2019).","journal-title":"Front. Immunol."},{"key":"34794_CR27","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/s41593-023-01257-z","volume":"26","author":"S De Schepper","year":"2023","unstructured":"De Schepper, S. et al. Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer\u2019s disease. Nat. Neurosci. 26, 406\u2013415. https:\/\/doi.org\/10.1038\/s41593-023-01257-z (2023).","journal-title":"Nat. Neurosci."},{"key":"34794_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109955","volume":"37","author":"L He","year":"2021","unstructured":"He, L. et al. Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors. Cell Rep. 37, 109955. https:\/\/doi.org\/10.1016\/j.celrep.2021.109955 (2021).","journal-title":"Cell Rep."},{"key":"34794_CR29","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1126\/science.ade2292","volume":"381","author":"R Bill","year":"2023","unstructured":"Bill, R. et al. CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers. Science 381, 515\u2013524. https:\/\/doi.org\/10.1126\/science.ade2292 (2023).","journal-title":"Science"},{"key":"34794_CR30","doi-asserted-by":"publisher","first-page":"5806602","DOI":"10.1155\/2021\/5806602","volume":"2021","author":"X Pang","year":"2021","unstructured":"Pang, X. et al. SPP1 promotes enzalutamide resistance and epithelial-mesenchymal-transition activation in castration-resistant prostate cancer via PI3K\/AKT and ERK1\/2 pathways. Oxid. Med. Cell. Longev. 2021, 5806602. https:\/\/doi.org\/10.1155\/2021\/5806602 (2021).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"34794_CR31","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.cell.2021.01.024","volume":"184","author":"S Ma","year":"2021","unstructured":"Ma, S. et al. A role of PIEZO1 in iron metabolism in mice and humans. Cell 184, 969-982.e913. https:\/\/doi.org\/10.1016\/j.cell.2021.01.024 (2021).","journal-title":"Cell"},{"key":"34794_CR32","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1111\/brv.12814","volume":"97","author":"A Lai","year":"2022","unstructured":"Lai, A. et al. Mechanosensing by Piezo1 and its implications for physiology and various pathologies. Biol Rev Camb Philos Soc 97, 604\u2013614. https:\/\/doi.org\/10.1111\/brv.12814 (2022).","journal-title":"Biol Rev Camb Philos Soc"},{"key":"34794_CR33","doi-asserted-by":"publisher","first-page":"1149336","DOI":"10.3389\/fimmu.2023.1149336","volume":"14","author":"Y Tang","year":"2023","unstructured":"Tang, Y. et al. Mechanosensitive Piezo1 protein as a novel regulator in macrophages and macrophage-mediated inflammatory diseases. Front. Immunol. 14, 1149336. https:\/\/doi.org\/10.3389\/fimmu.2023.1149336 (2023).","journal-title":"Front. Immunol."},{"key":"34794_CR34","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.2147\/jir.S495987","volume":"18","author":"L Wu","year":"2025","unstructured":"Wu, L., Huang, J., Jia, X. & Mao, X. Role and mechanism of mitochondrial ribosomal proteins in septic myocardial injury. J. Inflamm. Res. 18, 2677\u20132698. https:\/\/doi.org\/10.2147\/jir.S495987 (2025).","journal-title":"J. Inflamm. Res."},{"key":"34794_CR35","doi-asserted-by":"publisher","first-page":"17434","DOI":"10.1038\/s41598-017-16363-9","volume":"7","author":"K Svennerholm","year":"2017","unstructured":"Svennerholm, K. et al. Escherichia coli outer membrane vesicles can contribute to sepsis induced cardiac dysfunction. Sci. Rep. 7, 17434. https:\/\/doi.org\/10.1038\/s41598-017-16363-9 (2017).","journal-title":"Sci. Rep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34794-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34794-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34794-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T22:03:25Z","timestamp":1770242605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34794-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["34794"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-34794-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6737272\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"assertion":[{"value":"24 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study has been approved by the Institutional Committee on Animal Care of Capital Medical University (Protocol number A5095F17-EA0D-4377-88F7-FED2CE3A2ED2).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"4879"}}