{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:37Z","timestamp":1791561037457,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102674"],"award-info":[{"award-number":["82102674"]}],"id":[{"id":"10.13039\/501100001809","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>Previous studies have highlighted the significance of the bile acid receptor TGR5 (also known as Takeda G protein\u2010coupled receptor 5) in regulating inflammation and mitochondrial homeostasis in various diseases, whereas the specific involvement of TGR5 in spinal cord injury (SCI) remains unclear. This study aimed to elucidate the effects of TGR5 on SCI, as well as the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The TGR5 agonist INT\u2010777 was used to activate TGR5 in a mouse model of SCI, induced by contusion injury to T9\u2010T10 vertebrae, and cultured cells. To determine the mechanism of TGR5 activation after SCI, public dataset analysis, behaviour assessment, histology and biochemical analysis relating to inflammation, pyroptosis and mitochondrial function were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>TGR5 levels were increased in a mouse model of spinal cord injury (SCI), and in primary microglia and BV2 cells treated with tert\u2010butyl hydroperoxide. Furthermore, TGR5 activation by INT\u2010777 improved functional recovery and tissue repair in SCI mice. Mechanistically, INT\u2010777\u2010mediated TGR5 activation exerted a neuroprotective effect by regulating cAMP\/AMPK signalling, resulted in suppression of mitochondrial dysfunction and mitochondrial DNA (mtDNA) release, which inhibited absent in melanoma 2 (AIM2)\u2010driven pyroptosis and the inflammatory response. Notably, AIM2 overexpression partly blocked the neuroprotective effects of TGR5 activation in SCI mice. Additionally, AMPK inhibition by dorsomorphin aggravated neural injury and inflammation was alleviated in AIM2 deletion mice following SCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>INT\u2010777 exerts anti\u2010inflammatory and neuroprotective effects in the injured spinal cord by activating the TGR5\/cAMP\/AMPK pathway, thereby maintaining mitochondrial homeostasis and suppressing AIM2\u2010mediated pyroptosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70619","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:59:03Z","timestamp":1785801543000},"page":"6458-6480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The bile acid receptor TGR5 promotes functional recovery after spinal cord injury by rescuing mitochondrial dysfunction and suppressing AIM2\u2010mediated pyroptosis"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2354-7508","authenticated-orcid":false,"given":"Yikang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7806-7094","authenticated-orcid":false,"given":"Yige","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1418-8822","authenticated-orcid":false,"given":"Nongtao","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6990-5833","authenticated-orcid":false,"given":"Jiawei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4762-1628","authenticated-orcid":false,"given":"Yangyi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8122-5544","authenticated-orcid":false,"given":"Xiangji","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-4881","authenticated-orcid":false,"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shenzhen Luohu Hospitial Group Luohu People's Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4227-1752","authenticated-orcid":false,"given":"Haihong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Qingtian People's Hospital  Lishui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2020-1921","authenticated-orcid":false,"given":"Yaosen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2964-8172","authenticated-orcid":false,"given":"Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"The Second Clinical Medical College Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70230"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70234"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70233"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70229"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15727"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01017-w"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155584"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323916"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-520-0_4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00662-0"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00436-x"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.114950"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.09.008"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200463R"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109726"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.09.016"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado1855"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03503-8"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.05.038"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.02.019"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06111-5"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.07.011"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113273"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14101270"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-03182-x"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70134"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15193"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1176-9"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.151671"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(16)30155-3"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.08.001"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02068-0"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.101882"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2014121271"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102530"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102322"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-03936-9"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.08.026"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.269"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102767"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.11.021"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03363-0"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70619","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70619","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70619","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:07:25Z","timestamp":1791558445000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":45,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/bph.70619"],"URL":"https:\/\/doi.org\/10.1111\/bph.70619","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]},"assertion":[{"value":"2025-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}