{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:35:42Z","timestamp":1790505342854,"version":"4.1.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"13-14","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>Microglia-mediated neuroinflammatory responses play important roles in secondary neurological injury after traumatic brain injury (TBI). The TGF-\u03b2 pathway participates in the regulation of M1\/M2 phenotype transformation of microglia. TGF-\u03b2 can activate the Smad pathway by binding to TGF-\u03b2Rs, which is regulated by the cleavage function of A disintegrin and metalloproteinase 17 (ADAM17). However, the role of ADAM17 and the associated signaling pathways in the pathological process after TBI remain unclear. Herein, we assessed the transformation of microglia M1\/M2 phenotype polarization and the neuroinflammatory response after the inhibition of ADAM17. The formation of TGF-\u03b2Rs and TGF-\u03b21\/TGF-\u03b2RII complexes on microglia were detected to evaluate the effect of ADAM17 inhibition on the TGF-\u03b21\/Smad pathway. ADAM17 was highly expressed after TBI and mainly located in the microglia. the inhibition of ADAM17 improved neurological function after TBI. The neuroprotective effect of ADAM17 inhibition was related to a shift from the M1 microglial phenotype to the M2 microglial phenotype, thus reducing TBI-induced neuroinflammation. ADAM17 inhibition increased expression of TGF-\u03b2Rs on the microglia membrane, promoted formation of TGF-\u03b21\/TGF-\u03b2RII complexes, and induced intranuclear translocation of Smads, which activated the TGF-\u03b2\/Smad pathway. In conclusion, our study suggested that ADAM17 inhibition regulated microglia M1\/M2 phenotype polarization through the TGF-\u03b21\/Smad pathway and influenced the neuroinflammatory response after TBI.<\/jats:p>","DOI":"10.1089\/neu.2022.0373","type":"journal-article","created":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T11:12:06Z","timestamp":1680952326000},"page":"1495-1509","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["ADAM17 Aggravates the Inflammatory Response by Modulating Microglia Polarization Through the TGF-\u03b21\/Smad Pathway Following Experimental Traumatic Brain Injury"],"prefix":"10.1177","volume":"40","author":[{"given":"Xiangrong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, China."},{"name":"Fujian Institutes of Brain Disorders and Brain Science, Fuzong Clinical 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