{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:27Z","timestamp":1791561027754,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["JJ2020LH0293"],"award-info":[{"award-number":["JJ2020LH0293"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Our previous study has highlighted the anti\u2010inflammatory properties of gabapentin (GBP) after myocardial infarction (MI) by suppressing M1 macrophage polarization. In this study, we further dissected the important molecules involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Ligation of the left anterior descending coronary artery was used to construct the MI mouse model. Tyrosine\u2010protein phosphatase non\u2010receptor type 2 (PTPN2) expression in mouse myocardial tissue macrophages was evaluated using Western blot and dual\u2010labelling immunofluorescence. An MI mouse model with macrophage\u2010specific knockdown of PTPN2 was constructed and treated with GBP. M1 polarization was induced by lipopolysaccharide (LPS) and IFN\u2010\n                      <jats:italic>\u03b3<\/jats:italic>\n                      in mouse RAW264.7 cells and bone marrow\u2010derived macrophages. Substrates of PTPN2 were predicted and verified using co\u2010IP and amino acid mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>GBP alleviated cardiac dysfunction and reduced myocardial injury and macrophage M1 polarization in mice. PTPN2 expression was increased in macrophages of mice induced with MI in response to the inflammatory response, and GBP further up\u2010regulated PTPN2. Macrophage depletion impaired the efficacy of GBP. PTPN2 knockdown enhanced M1 polarization of macrophages and exacerbated cardiac dysfunction in mice. The binding of PTPN2 to 7\u2010dehydrocholesterol reductase (DHCR7) inhibited Y378 phosphorylation of DHCR7 and reduced the cholesterol synthesis catalysed by DHCR7. DHCR7 knockdown in macrophages reversed macrophage pro\u2010inflammatory activation induced by PTPN2 knockdown, alleviated myocardial injury in mice and restored the efficacy of GBP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>GBP enhances PTPN2 expression to inhibit tyrosine phosphorylation of DHCR7 and blocks cholesterol metabolism to limit macrophage M1 polarization and alleviate MI\u2010induced injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70609","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T01:00:25Z","timestamp":1785286825000},"page":"6306-6328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tyrosine\u2010protein phosphatase non\u2010receptor type 2 deficiency in macrophages diminishes the anti\u2010inflammatory and cardioprotective effects of gabapentin after myocardial infarction"],"prefix":"10.1111","volume":"183","author":[{"given":"Zhenjun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Cardiology First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaojun","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Cardiology First Affiliated Hospital of Harbin Medical University  Harbin Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology First Affiliated Hospital of Harbin Medical University  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