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Controlling ER stress through genetic intervention is a promising approach for treating vascular calcification. In this study, we demonstrated a positive correlation between ER stress\u2013induced tribble homolog 3 (\n                    <jats:italic>TRIB3<\/jats:italic>\n                    ) expression and progression of vascular calcification in human and rodent CKD. Increased\n                    <jats:italic>TRIB3<\/jats:italic>\n                    expression promoted vascular smooth muscle cell (VSMC) calcification by interacting with the C2 domain of the E3 ubiquitin-protein ligase Smurf1, facilitating its K48-related self-ubiquitination at Lys381 and Lys383 and subsequent dissociation from the plasma membrane and nuclei. This degeneration of Smurf1 accelerated the stabilization of the osteogenic transcription factors RUNX family transcription factor 2 (Runx2) and SMAD family member 1 (Smad1). C\/EBP homologous protein and activating transcription factor 4 are upstream transcription factors of\n                    <jats:italic>TRIB3<\/jats:italic>\n                    in an osteogenic environment. Genetic KO of\n                    <jats:italic>TRIB3<\/jats:italic>\n                    or rescue of Smurf1 ameliorated VSMC and vascular calcification by stabilizing Smurf1 and enhancing the degradation of Runx2 and Smad1. Our findings shed light on the vital role of\n                    <jats:italic>TRIB3<\/jats:italic>\n                    as a scaffold in ER stress and vascular calcification and offer a potential therapeutic option for CKD.\n                  <\/jats:p>","DOI":"10.1172\/jci175972","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T12:00:37Z","timestamp":1739275237000},"source":"Crossref","is-referenced-by-count":13,"title":["TRIB3 mediates vascular calcification by facilitating self-ubiquitination and dissociation of Smurf1 in chronic kidney disease"],"prefix":"10.1172","volume":"135","author":[{"given":"Yihui","family":"Li","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, Qilu Hospital of Shandong University, Jinan, China."},{"name":"Department of Critical Care Medicine, Qilu Hospital, Innovation Research Center for Sepsis and Multiple Organ Injury, Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-5598","authenticated-orcid":true,"given":"Chang","family":"Ma","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, Qilu Hospital of Shandong University, Jinan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Sheng","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, Qilu Hospital of Shandong University, Jinan, 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