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Open Access | 10.1172/JCI175972
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Li, Y. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
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1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Sheng, Y. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Huang, S. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Sun, H. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Ti, Y. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Wang, Z. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Wang, F. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Chen, F. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Li, C. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Guo, H. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Tang, M. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Song, F. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Wang, H. in: JCI | PubMed | Google Scholar
1State Key Laboratory for Innovation and Transformation of Luobing Theory, D, Qilu Hospital of Shandong University, Jinan, China
2Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China
3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
4Department of Critical Care Medicine, Shandong Provincial Hospital, Jinan, China
5Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Jinan, China
6Department of Critical Care Medicine, Qilu Hospital; Innovation Research Ce, Shandong University, Jinan, China
7Department of Emergency, Qilu Hospital of Shandong University, Jinan, China
8Department of Critical Care Medicine, The Affiliated Tengzhou Hospital of Xuzhou Medical University/ Tengzhou Central People's Hospital, Xuzhou, China
Find articles by Zhong, M. in: JCI | PubMed | Google Scholar
Published February 11, 2025 - More info
The osteogenic environment promotes vascular calcium phosphate deposition and aggregation of unfolded and misfolded proteins, resulting in endoplasmic reticulum (ER) stress in chronic renal disease (CKD). 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-induced tribble 3 (TRIB3) expression and progression of vascular calcification in human and rodent CKD. Increased TRIB3 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 TRIB3 in an osteogenic environment. Genetic knockout of TRIB3 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 TRIB3 as a scaffold in ER stress and vascular calcification and offer a potential therapeutic option for chronic renal disease.