{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T01:55:47Z","timestamp":1768614947768,"version":"3.49.0"},"reference-count":27,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hebei Province Natural Science Foundation Precision Medicine Innovation and Development Joint Fund Cultivation Project","award":["H2025405071"],"award-info":[{"award-number":["H2025405071"]}]},{"name":"Hebei Province Natural Science Foundation Precision Medicine Innovation and Development Joint Fund Cultivation Project","award":["202410092009"],"award-info":[{"award-number":["202410092009"]}]},{"name":"Hebei Province Natural Science Foundation Precision Medicine Innovation and Development Joint Fund Cultivation Project","award":["82270524"],"award-info":[{"award-number":["82270524"]}]},{"name":"Hebei Province National College Student Innovation and Entrepreneurship Training Project","award":["H2025405071"],"award-info":[{"award-number":["H2025405071"]}]},{"name":"Hebei Province National College Student Innovation and Entrepreneurship Training Project","award":["202410092009"],"award-info":[{"award-number":["202410092009"]}]},{"name":"Hebei Province National College Student Innovation and Entrepreneurship Training Project","award":["82270524"],"award-info":[{"award-number":["82270524"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["H2025405071"],"award-info":[{"award-number":["H2025405071"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["202410092009"],"award-info":[{"award-number":["202410092009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82270524"],"award-info":[{"award-number":["82270524"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Cir. Bras."],"abstract":"<jats:p>ABSTRACT  Purpose: Acute lung injury is the most severe complication of hemorrhagic shock and closely correlates with the mortality rate of hemorrhagic shock. TIPE2 is a critical regulator of inflammation and is implicated in the pathogenesis of various inflammatory diseases. However, its role in hemorrhagic shock-induced acute lung injury is unclear, and the underlying mechanisms remain to be elucidated. Therefore, the purpose of this study was to investigate the role of TIPE2 in hemorrhagic shock-induced acute lung injury and its underlying mechanisms.  Methods: C57BL\/6J and TIPE2 knockout mice were used to establish hemorrhagic shock model, with a sham surgery as the control. The pulmonary ventilation function was evaluated using in-vivo testing system. Blood gas analysis was conducted to evaluate changes in blood oxygen level, reflecting the body\u2019s acid-base balance. Hematoxylin and eosin staining facilitated the observation of lesion progression in pulmonary tissue. The expression levels of TIPE2, myeloperoxidase, and citrullinated histone in lung tissues were determined by Western blotting, whereas the levels of tumor necrosis factor-\u03b1 and IFN-\u03b3 in bronchoalveolar lavage fluid were quantified by enzyme-linked immunosorbent assay to evaluate the levels of key inflammatory mediators. VE-cadherin and E-cadherin expression in lung tissues were assessed by Western blotting to indicate changes of lung microvascular and alveolar permeability.  Results: Following hemorrhagic shock, mice developed severe acute lung injury, characterized by impaired lung function, respiratory acidosis, structural damage, and pulmonary edema. This was accompanied by a heightened inflammatory response, evidenced by elevated neutrophil activity and pro-inflammatory cytokines, alongside impaired endothelial and epithelial barrier integrity. Notably, TIPE2 knockout conferred protection against hemorrhagic shock-induced lung injury in mice.  Conclusion: TIPE2 knockout attenuates hemorrhagic shock-induced acute lung injury through mechanisms involving downregulation of inflammatory-associated protein expression, suppression of proinflammatory cytokine release, and restoration of pulmonary barrier permeability.<\/jats:p>","DOI":"10.1590\/acb410326","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T15:01:56Z","timestamp":1768575716000},"source":"Crossref","is-referenced-by-count":0,"title":["The role of TIPE2 in hemorrhagic shock-induced acute lung injury"],"prefix":"10.1590","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5977-4824","authenticated-orcid":false,"given":"Yu-Ying","family":"Rong","sequence":"first","affiliation":[{"name":"Hebei North University,  China; Hebei North University,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8087-1158","authenticated-orcid":false,"given":"Yuan-Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei North University,  China; Hebei North University,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5054-916X","authenticated-orcid":false,"given":"Shi-Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Hebei North University,  China; Hebei North University,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3527-4305","authenticated-orcid":false,"given":"Shu-Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Hebei North University,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6540-0038","authenticated-orcid":false,"given":"Yue-Hong","family":"Dong","sequence":"additional","affiliation":[{"name":"Hebei North University,  China; Hebei North University,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5726-1250","authenticated-orcid":false,"given":"Hui-Bo","family":"Du","sequence":"additional","affiliation":[{"name":"Hebei North University,  China; Hebei Key Laboratory of Critical Disease Mechanism and Intervention,  China; Key Laboratory of Microcirculation and Shock,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5963-740X","authenticated-orcid":false,"given":"Xiu","family":"Xu","sequence":"additional","affiliation":[{"name":"Hebei North University,  China; Hebei Key Laboratory of Critical Disease Mechanism and Intervention,  China; Key Laboratory of Microcirculation and Shock,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9434-5231","authenticated-orcid":false,"given":"Zi-Gang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hebei North University,  China; Hebei Key Laboratory of Critical Disease Mechanism and Intervention,  China; Key Laboratory of Microcirculation and Shock,  China; Zhangjiakou University,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9314-0288","authenticated-orcid":false,"given":"Li-Na","family":"Jiang","sequence":"additional","affiliation":[{"name":"Hebei North University,  China; Hebei North University,  China; Hebei Key Laboratory of Critical Disease Mechanism and Intervention,  China; Key Laboratory of Microcirculation and Shock,  China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"530","published-online":{"date-parts":[[2026]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"749659","DOI":"10.3389\/fimmu.2021.749659","article-title":"Therapeutic potential of mesenchymal stromal cell-derived extracellular vesicles in the prevention of organ injuries induced by traumatic hemorrhagic shock","volume":"12","author":"Valade G","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"ref2","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12931-023-02429-y","article-title":"Ferroptosis-related signature and immune infiltration characterization in acute lung injury\/acute respiratory distress syndrome","volume":"24","author":"Ma A","year":"2023","journal-title":"Respir Res"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.3389\/fimmu.2020.01722","article-title":"Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury","volume":"11","author":"Kumar V.","year":"2020","journal-title":"Front Immunol"},{"issue":"5","key":"ref4","doi-asserted-by":"crossref","first-page":"100777","DOI":"10.1016\/j.cpsurg.2020.100777","article-title":"Acute lung injury","volume":"57","author":"Mowery NT","year":"2020","journal-title":"Curr Probl Surg"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/SHK.0000000000002064","article-title":"Valproic acid inhibits classical monocyte-derived tissue factor and alleviates hemorrhagic shock-induced acute lung injury in rats","volume":"59","author":"Shao L","year":"2023","journal-title":"Shock"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"105224","DOI":"10.1016\/j.phrs.2020.105224","article-title":"Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms","volume":"163","author":"He YQ","year":"2021","journal-title":"Pharmacol Res"},{"issue":"8","key":"ref7","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1172\/JCI60331","article-title":"The acute respiratory distress syndrome","volume":"122","author":"Matthay MA","year":"2012","journal-title":"J Clin Invest"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"838618","DOI":"10.3389\/fimmu.2022.838618","article-title":"TLR2\/TLR4-enhanced TIPE2 expression is involved in post-hemorrhagic shock mesenteric lymph-induced activation of CD4+T cells","volume":"13","author":"Du HB","year":"2022","journal-title":"Front Immunol"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3109\/0886022X.2015.1105026","article-title":"Inhibitory effect of post-hemorrhagic shock mesenteric lymph drainage on the HMGB1 and RAGE in mouse kidney","volume":"38","author":"Liu GQ","year":"2016","journal-title":"Ren Fail"},{"issue":"5","key":"ref10","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1097\/SHK.0000000000002102","article-title":"Estrogen alleviates posthemorrhagic shock mesenteric lymph-mediated lung injury through autophagy inhibition","volume":"59","author":"Sun Q","year":"2023","journal-title":"Shock"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00134-003-2001-y","article-title":"Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide","volume":"30","author":"Su X","year":"2004","journal-title":"Intensive Care Med"},{"issue":"6","key":"ref12","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14813","article-title":"Hemorrhagic shock and fluid dynamics","volume":"9","author":"Cohen M","year":"2021","journal-title":"Physiol Rep"},{"issue":"Suppl.3","key":"ref13","article-title":"Acute lung injury: from pathophysiology to treatment","volume":"69","author":"Mokr\u00e1 D","year":"2020","journal-title":"Physiol Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"918380","DOI":"10.3389\/fimmu.2022.918380","article-title":"Innate immunity and immunotherapy for hemorrhagic shock","volume":"13","author":"Huang Q","year":"2022","journal-title":"Front Immunol"},{"issue":"8","key":"ref15","first-page":"936","article-title":"TIPE2 is essential for apocynin-mediated protection against intestinal ischemia\/reperfusion-induced acute lung injury","volume":"37","author":"Jing HR","year":"2024","journal-title":"Biomed Environ Ci"},{"key":"ref16","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/1264913","article-title":"The role of macrophages in the pathogenesis of ALI\/ARDS","volume":"2018","author":"Huang X","year":"2018","journal-title":"Mediators Inflamm"},{"issue":"2","key":"ref17","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.apsb.2021.08.009","article-title":"Pulmonary delivery of siRNA against acute lung injury\/acute respiratory distress syndrome","volume":"12","author":"Zoulikha M","year":"2022","journal-title":"Acta Pharm Sin B"},{"issue":"39","key":"ref18","doi-asserted-by":"crossref","first-page":"32546","DOI":"10.1074\/jbc.M112.348755","article-title":"TIPE2, a novel regulator of immunity, protects against experimental stroke","volume":"287","author":"Zhang Y","year":"2012","journal-title":"J Biol Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.3389\/fimmu.2019.02284","article-title":"Loss of TIPE2 has opposing effects on the pathogenesis of autoimmune diseases","volume":"10","author":"Liu R","year":"2019","journal-title":"Front Immunol"},{"issue":"12","key":"ref20","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1038\/ni.3866","article-title":"Direction of leukocyte polarization and migration by the phosphoinositide-transfer protein TIPE2","volume":"18","author":"Fayngerts SA","year":"2017","journal-title":"Nat Immunol"},{"issue":"2","key":"ref21","article-title":"TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis","volume":"217","author":"Yan D","year":"2020","journal-title":"J Exp Med"},{"issue":"38","key":"ref22","article-title":"TIPE2 is a checkpoint of natural killer cell maturation and antitumor immunity","volume":"7","author":"Bi J","year":"2021","journal-title":"Sci Adv"},{"issue":"12","key":"ref23","article-title":"Checkpoint TIPE2 limits the helper functions of NK cells in supporting antitumor CD8+ T cells","volume":"10","author":"Bi J","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"761981","DOI":"10.3389\/fimmu.2021.761981","article-title":"Interaction between commensal bacteria, immune response and the intestinal barrier in inflammatory bowel disease","volume":"12","author":"Chen Y","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"114287","DOI":"10.1016\/j.yexcr.2024.114287","article-title":"TIPE2 aggravates experimental colitis and disrupts intestinal epithelial barrier integrity by activating JAK2\/STAT3\/SOCS3 signal pathway","volume":"443","author":"Zeng L","year":"2024","journal-title":"Exp Cell Res"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1158\/2326-6066.CIR-21-0666","article-title":"Tumor necrosis factor-alpha-induced protein 8-like 2 fosters tumor-associated microbiota to promote the development of colorectal cancer","volume":"10","author":"Lou Y-W","year":"2022","journal-title":"Cancer Immunol Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1089099","DOI":"10.3389\/fmed.2023.1089099","article-title":"JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases","volume":"10","author":"Herrera-deGuise C","year":"2023","journal-title":"Front Med (Lausanne)"}],"container-title":["Acta Cir\u00fargica Brasileira"],"original-title":[],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S0102-86502026000100602&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T15:02:01Z","timestamp":1768575721000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S0102-86502026000100602&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":27,"alternative-id":["S0102-86502026000100602"],"URL":"https:\/\/doi.org\/10.1590\/acb410326","relation":{},"ISSN":["1678-2674","0102-8650"],"issn-type":[{"value":"1678-2674","type":"electronic"},{"value":"0102-8650","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"e410326"}}