{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T14:23:32Z","timestamp":1777731812509,"version":"3.51.4"},"reference-count":28,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Sepsis is a complex clinical syndrome with high incidence and mortality. Acute lung injury (ALI) is a common complication of sepsis. At present, there is no effective therapeutic strategy to treat ALI. The SET domain\u2013containing histone methyltransferase Wolf\u2013Hirschhorn syndrome candidate 1 (WHSC1) regulates cancer progression, while its role in sepsis-induced ALI remains unclear. Thus, this study aimed to study the effect of WHSC1 on sepsis-induced ALI and to explore the potential mechanism of action. In the study, LPS treatment induced lung injury. WHSC1 was highly expressed in LPS-induced ALI. Knockdown of WHSC1 attenuated LPS-induced ALI and pyroptosis in vivo. Besides, knockdown of WHSC1 attenuated LPS-induced alveolar macrophage pyroptosis in vitro. Furthermore, NIMA-related kinase-7 (NEK7) expression could be regulated by WHSC1, and NEK7 bound to NLRP3 in alveolar macrophages. Moreover, WHSC1 regulated alveolar macrophage pyroptosis through modulating NEK7-mediated NLRP3 inflammasome activation. In conclusion, WHSC1 was highly expressed in LPS-induced ALI. WHSC1 facilitated alveolar macrophage pyroptosis in sepsis-induced ALI through NEK7-mediated NLRP3 inflammasome activation. WHSC1 may be a valuable target for the therapy of sepsis-induced ALI.<\/jats:p>","DOI":"10.1177\/17534259211035426","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T03:49:59Z","timestamp":1629863399000},"page":"437-447","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Wolf\u2013Hirschhorn syndrome candidate 1 facilitates alveolar macrophage pyroptosis in sepsis-induced acute lung injury through NEK7-mediated NLRP3 inflammasome activation"],"prefix":"10.1177","volume":"27","author":[{"given":"Caixia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Taihe Hospital, Hubei University of Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benlong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Taihe Hospital, Hubei University of Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Taihe Hospital, Hubei University of Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-5765","authenticated-orcid":false,"given":"Yuan","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Taihe Hospital, Hubei University of Medicine, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"bibr1-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2012"},{"key":"bibr2-17534259211035426","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.621663"},{"key":"bibr3-17534259211035426","first-page":"629","volume":"92","author":"Caraballo C","year":"2019","journal-title":"The Yale Journal of Biology and Medicine"},{"key":"bibr4-17534259211035426","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.590652"},{"key":"bibr5-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-019-00990-7"},{"key":"bibr6-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2070"},{"key":"bibr7-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1761-4"},{"key":"bibr8-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.139"},{"key":"bibr9-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.106175"},{"key":"bibr10-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.08.054"},{"key":"bibr11-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165685"},{"key":"bibr12-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000595"},{"key":"bibr13-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.7.1071"},{"key":"bibr14-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5638-9"},{"key":"bibr15-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-14-0292-T"},{"key":"bibr16-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2157-1"},{"key":"bibr17-17534259211035426","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S204701"},{"key":"bibr18-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91144"},{"key":"bibr19-17534259211035426","doi-asserted-by":"publisher","DOI":"10.3892\/or.2017.5463"},{"key":"bibr20-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-9078-2_1"},{"key":"bibr21-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.5b00609"},{"key":"bibr22-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105741"},{"key":"bibr23-17534259211035426","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.144969"},{"key":"bibr24-17534259211035426","doi-asserted-by":"crossref","unstructured":"Ding H, Yang J, Chen L, et\u00a0al. Memantine alleviates acute lung injury via inhibiting macrophage pyroptosis.\n                      Shock\n                      . Epub ahead of print 13 April 2021. 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