{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:44:41Z","timestamp":1792133081070,"version":"4.4.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2408085MH234"],"award-info":[{"award-number":["2408085MH234"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"\n Background and purpose<\/jats:title>\n Septic encephalopathy (SE) is closely associated with disruption of blood\u2013brain barrier (BBB), resulting in neurological deficits and poor clinical outcomes. Protein tyrosine phosphatase receptor type O (PTPRO) regulates disease states by dephosphorylating membrane\u2010associated proteins and modulating intracellular signalling. Here we have examined the role of PTPRO in regulating BBB permeability and have assessed a PTPRO inhibitor (Pi) in mitigating BBB disruption during endotoxemia\u2010associated encephalopathy.<\/jats:p>\n <\/jats:sec>\n \n Experimental approach<\/jats:title>\n Genetic and pharmacological approaches, including PTPRO overexpression, knockdown or deficiency and Pi treatment, were used to evaluate endothelial dysfunction in bEND.3 cells, primary mouse brain microvascular endothelial cells and an LPS\u2010induced murine model of endotoxemia\u2010associated encephalopathy. Barrier dysfunction, cytoskeletal remodelling and signalling events were assessed using permeability assays, immunoblotting, immunofluorescence and in vivo BBB leakage analyses.<\/jats:p>\n <\/jats:sec>\n \n Key results<\/jats:title>\n LPS increased PTPRO expression in brain tissue from endotoxemic mice and cerebral endothelial cells. Elevated PTPRO promoted F\u2010actin reorganization, stress fibre formation and intercellular gap formation, whereas Pi treatment or PTPRO silencing attenuated these changes. PTPRO overexpression worsened endothelial barrier dysfunction, while Pi reduced thrombin\u2010induced permeability in bEND.3 cells and wild\u2010type primary endothelial cells. Primary endothelial cells from PTPRO\u2010deficient mice were protected. Mechanistically, PTPRO regulated cytoskeletal dynamics through the ErbB2\u2010Rho\u2010MLC2 pathway. In vivo, Pi treatment and PTPRO deficiency reduced BBB leakage, with limited effects on inflammatory cytokines.<\/jats:p>\n <\/jats:sec>\n \n Conclusion and implications<\/jats:title>\n These findings identify PTPRO as an important regulator of BBB disruption in endotoxemia\u2010associated encephalopathy and support pharmacological targeting of PTPRO as a potential strategy for preserving sepsis\u2010associated BBB injury.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.70682","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:49:54Z","timestamp":1792129794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A PTPRO inhibitor Pi mitigates endotoxemia\u2010induced encephalopathy\u2010mediated blood\u2013brain barrier disruption through cytoskeletal regulation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8539-8686","authenticated-orcid":false,"given":"Fengjiao","family":"Wu","sequence":"first","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of Basic and Translational Research of Inflammation\u2010Related Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4455-1918","authenticated-orcid":false,"given":"Haitao","family":"Tang","sequence":"additional","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of Basic and Translational Research of Inflammation\u2010Related Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2145-3190","authenticated-orcid":false,"given":"Qianqian","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Nanjing Meishan Hospital Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5240-9177","authenticated-orcid":false,"given":"Jing","family":"Shi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of Basic and Translational Research of Inflammation\u2010Related Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5232-6460","authenticated-orcid":false,"given":"Chang","family":"Li","sequence":"additional","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of Basic and Translational Research of Inflammation\u2010Related Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3787-5083","authenticated-orcid":false,"given":"Jun","family":"Qian","sequence":"additional","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of Basic and Translational Research of Inflammation\u2010Related Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0907-683X","authenticated-orcid":false,"given":"Haoxuan","family":"Jia","sequence":"additional","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of Basic and Translational Research of Inflammation\u2010Related Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0084-2230","authenticated-orcid":false,"given":"Jiwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of Basic and Translational Research of Inflammation\u2010Related Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Immunology, School of Basic Medical Sciences, Bengbu Medical University Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9695-9572","authenticated-orcid":false,"given":"Qingqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Interdisciplinary Eye Research Institute (EYE\u2010X Institute), Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Province Key Laboratory of 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