{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:37:42Z","timestamp":1792723062401,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Microglial polarization shifts that induce inflammatory responses play a role in the occurrence and progression of spinal cord injury (SCI). We reported that checkpoint kinase 1 (Chk1) was involved in regulating SCI\u2010induced motor dysfunction. We aim now to determine whether the microglial polarization shift is involved in the action of Chk1 on SCI\u2010induced motor dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The pathological SCI\n                      <jats:italic>in vivo<\/jats:italic>\n                      model was induced in mice through spinal cord contusion injury, while the\n                      <jats:italic>in vitro<\/jats:italic>\n                      model was established by exposing cultured murine BV2 cells to lipopolysaccharide (LPS). To analyse the expression levels of associated genes and proteins, we utilized quantitative real\u2010time polymerase chain reaction, western blotting and immunofluorescence staining. We employed the cell counting kit\u20108, EdU assay and comet assay to evaluate microglia proliferation and DNA damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Chk1<\/jats:italic>\n                      down\u2010regulation reversed the shift in microglial polarization and pyroptosis induced by SCI\n                      <jats:italic>in vivo<\/jats:italic>\n                      , improving motor dysfunction. Up\u2010regulation of\n                      <jats:italic>Chk1<\/jats:italic>\n                      worsened the microglial polarization shift and pyroptosis, causing deterioration in motor function following SCI.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , both\n                      <jats:italic>\u03b3<\/jats:italic>\n                      \u2010H2AX and Chk1 activation increased in BV2 cells in a dose\u2010 and time\u2010dependent manner in response to LPS. The selective Chk1 inhibitor SCH900776 or the DNA damage repair agonist AV\u2010153 showed that LPS\u2010induced microglial polarization shifted from M2 to M1 and this shift was linked to the suppression of pyroptosis signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Our results demonstrate that the Chk1\u2010regulated shift in microglial polarization through pyroptosis signalling may be a promising drug target for future therapies for SCI\u2010induced motor dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70716","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:46:17Z","timestamp":1792719977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Checkpoint kinase 1 (Chk1) inhibition promotes motor function recovery through suppressing pyroptosis signalling and attenuating microglial polarization shift to M1 phenotype in spinal cord injury mice"],"prefix":"10.1111","author":[{"given":"Mengfan","family":"Chen","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziheng","family":"Fang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Du","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"},{"name":"College of Pharmaceutical Sciences Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Lian","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhong","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maolin","family":"Qin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuo","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulun","family":"Wu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshe","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Kong","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou China"},{"name":"Cixi Biomedical Research Institute Wenzhou Medical University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junming","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Wenzhou Medical University  Wenzhou China"},{"name":"Cixi Biomedical Research Institute Wenzhou Medical University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2020.08.004"},{"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.14112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207533"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03656-6"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719856115"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00287-9"},{"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":"10.4103\/NRR.NRR-D-23-01925"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689718755778"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112521"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-23-01256"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-023-00967-y"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-02255-w"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.815347"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109616"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02960-x"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14221"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2021.1912040"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-020-09920-z"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.389302"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.901117"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1067\/mva.2003.150"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c02379"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01958-2"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110103"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.84564"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3469"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13139"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-018-1008-3"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114586"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12992"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13387"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-9070-5"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101781"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.894"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-023-03930-y"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.355747"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110853"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-024-04678-z"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.269"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1818758"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03495-3"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167141"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03208-y"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-24-00112"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70716","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70716","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70716","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:46:18Z","timestamp":1792719978000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":49,"alternative-id":["10.1111\/bph.70716"],"URL":"https:\/\/doi.org\/10.1111\/bph.70716","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"2025-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bph.70716"}}