{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:24:19Z","timestamp":1789986259562,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Microglia\u2010mediated neuroinflammatory responses have a critical function in the spinal cord injury (SCI) mechanism, and targeted modulation of microglia activity has emerged as a new therapeutic strategy for SCI. Heme oxygenase 1(HO\u20101) regulates the close dynamic crosstalk between oxidative stress and inflammatory responses. This investigation aimed to study the molecular pathways by which HO\u20101 regulates the inflammatory response of microglia. We cultivated primary rat spinal cord microglia and BV2 cell lines and used lipopolysaccharide (LPS) to stimulate microglia to establish an in vitro model. The adeno\u2010associated virus (AAV) was used to induce HO\u20101 overexpression to observe the effects of HO\u20101 overexpression on microglia survival, morphological changes, microglia activation, inflammatory cytokines secretion, mitochondrial dynamics, and nucleotide\u2010binding oligomerization domain\u2010like receptor protein (NLRP3) inflammatory complex and nuclear factor\u2010\u03baB (NF\u2010\u03baB) signaling pathways. It was found that HO\u20101 overexpression was successfully induced using an AAV on microglia in vitro. HO\u20101 overexpression increased microglia survival and reduced microglia apoptosis in the inflammatory microenvironment. Overexpressed HO\u20101 inhibited microglia M1\u2010type polarization, downregulated the NF\u2010\u03baB signaling pathway, inhibited NLRP3 inflammatory complex activation, and reduced the secretion of inflammatory factors. Overexpressed HO\u20101 maintained the stability of mitochondrial dynamics and inhibited excessive mitochondrial cleavage. Further experiments showed that overexpression of HO\u20101 activated the interferon regulatory factor 1 (IRF1)\/dynamin\u2010related protein 1 (DRP1) signaling pathway, thereby promoting microglia M2\u2010type polarization and improving neuronal survival. This study demonstrates that HO\u20101 activates the IRF1\/DRP1 axis, promoting M2 polarization in microglia and attenuating neuroinflammation by suppressing the NF\u2010\u03baB signaling pathway. These outcomes offer new visions and important clues for effectively managing SCI in the clinic.<\/jats:p>","DOI":"10.1002\/ddr.70033","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T13:06:38Z","timestamp":1733922398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Heme Oxygenase\u20101 Overexpression Activates the IRF1\/DRP1 Signaling Pathway to Promote M2\u2010Type Polarization of Spinal Cord Microglia"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-5466","authenticated-orcid":false,"given":"Wenping","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Spine Surgery Shenzhen Pingle Orthopedic Hospital, Affiliated Hospital of Guangzhou University of Chinese Medicine Shenzhen 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