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Mounting evidences suggested that RNA-binding proteins (RBPs) exert pivotal roles in various diseases including AAA. The public human AAA microarray dataset and the RBP database were used to screen the involved RBPs during AAA formation. The integrated analysis identified zinc finger protein 36 (ZFP36) as a potential mediator of AAA. Underexpression of ZFP36 was observed in aortic vascular smooth muscle cells (VSMCs) within aneurysms from patients and angiotensin II (AngII)-induced mice.\n                    <jats:italic toggle=\"yes\">Zfp36<\/jats:italic>\n                    deficiency in VSMCs augmented extracellular matrix (ECM) degeneration, VSMC phenotypic switch, and apoptosis, which promoted AAA formation in the AngII-infused model. In contrast, VSMC-specific overexpressing\n                    <jats:italic toggle=\"yes\">Zfp36<\/jats:italic>\n                    inhibited AAA formation. Mechanically, guanylate binding protein 2 (GBP2), a GTPase related to interferon-\u03b3 signaling, was identified as a direct target gene of ZFP36 by analyzing the bulk sequencing data. We confirmed that ZFP36 regulates VSMC phenotypic switch via manipulating Yes-associated protein1\/TEA domain transcription factor 1 (YAP1\/TEAD1) signaling in a GBP2-dependent manner. Additionally, we further verified that dexamethasone (Dex) could promote glucocorticoid receptor nuclear translocation and\n                    <jats:italic toggle=\"yes\">Zfp36<\/jats:italic>\n                    transcription. In\u00a0vivo Dex administration prevented AAA formation in a ZFP36-dependent manner. These findings revealed the regulatory role of ZFP36\/GBP2\/YAP1\/TEAD1 signaling in VSMC phenotypic switch and AAA formation, and provided a novel strategy (Dex) for AAA treatment.\n                  <\/jats:p>","DOI":"10.34133\/research.1078","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T03:13:54Z","timestamp":1765854834000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":2,"title":["ZFP36 Protects against Abdominal Aortic Aneurysm Formation by Regulating Vascular Smooth Muscle Phenotypic Switch"],"prefix":"10.34133","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-1994","authenticated-orcid":false,"given":"Zhinan","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, \rQilu Hospital of Shandong University, Jinan 250012, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-2924","authenticated-orcid":false,"given":"Hanlin","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, \rQilu Hospital of Shandong University, Jinan 250012, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, \rQilu Hospital of Shandong University, Jinan 250012, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Yue","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research of MOE, NHC, CAMS and Shandong Province; Department of Cardiology, \rQilu Hospital of Shandong University, Jinan 250012, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Innovation and Transformation of Luobing Theory; 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