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Adv."],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:p>\n                    Macrophages play a key role in cardiac injury and repair after myocardial infarction (MI). Salt-inducible kinase 2 (SIK2), a member of the adenosine monophosphate\u2013activated protein kinase family, is notably up-regulated in monocytes\/macrophages of patients with MI and animal models. In this study, we investigated the role of SIK2 in macrophage-mediated inflammation and efferocytosis following MI. Macrophage-specific SIK2 deletion reduces infarct size and improves healing post-MI. Furthermore, SIK2-knockout macrophages decrease proinflammatory factor expression and enhance efferocytosis, thereby increasing repair factors expression. SIK2 associates with tumor necrosis factor receptor\u2013associated factor 2 (TRAF2), promoting its phosphorylation and K63 polyubiquitylation, which exacerbates inflammation and hinders efferocytosis via the P38 and nuclear factor \u03baB pathways. In contrast, the SIK2\n                    <jats:sup>T175A<\/jats:sup>\n                    mutation exhibits no effect. Macrophage-specific SIK2 overexpression worsens cardiac changes after MI, whereas P38 inhibition reduces this effect. In addition, pharmacological inactivation of SIK2 substantially enhances cardiac repair after MI in mice. These findings highlight the crucial role of macrophage SIK2 in the regulation of inflammation and efferocytosis via TRAF2 polyubiquitination in MI, thereby presenting potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adw6624","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:58:53Z","timestamp":1792173533000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["SIK2 antagonizes postinfarction cardiac repair by driving macrophage proinflammatory and impairing efferocytosis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0257-1678","authenticated-orcid":true,"given":"Wu-Wei","family":"Rong","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, National Research Center for Translational Medicine\u00b7Shanghai, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of 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