{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:38:58Z","timestamp":1777700338006,"version":"3.51.4"},"reference-count":32,"publisher":"IMR Press","issue":"4","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Foundation of China","doi-asserted-by":"crossref","award":["82170747"],"award-info":[{"award-number":["82170747"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Foundation of China","doi-asserted-by":"crossref","award":["82305095"],"award-info":[{"award-number":["82305095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Joint funding of the Kashgar Workstation of the State Key Laboratory of Causes and Prevention of High Incidence in Central Asia","award":["SKL-HIDCA2024-KS"],"award-info":[{"award-number":["SKL-HIDCA2024-KS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: As a predominant complication of chronic kidney disease (CKD), vascular calcification (VC) warrants investigation into its mechanisms. The epigenetic modulator Enhancer of Zeste Homologue 2 (EZH2) is implicated in various kidney disorders. This investigation aims to examine its function in the development of VC related to CKD. Methods: Radial arteries collected from individuals with kidney failure (with or without calcification) following arterial venous fistula surgery were processed for Von Kossa and immunohistochemical (IHC) staining. A VC- associated CKD model was established by administering a diet containing adenine and phosphate (1.2%) and 3-deazaneplanocin A (3-DZNeP) was used to block EZH2 activity. To induce calcification, thoracic aortas isolated from SD rats were cultured ex vivo in a medium containing 2.6 mmol\/L Pi. In parallel, an in vitro model of calcification was established by treating A7r5, a rat vascular smooth muscle cell line (VSMC), with a calcifying medium, and 3-DZNeP was used to inhibit EZH2. Adenovirus was used to overexpress EZH2 and siRNA was used to silence bone morphogenetic protein (BMP) 2. Results: EZH2 protein expression was higher in calcified arteries than in non-calcified arteries from individuals after the surgical creation of an arteriovenous fistula. In the mouse model, the upregulation of EZH2 and Runx2 at both the transcriptional and translational levels was demonstrated in calcified aortas. 3-DZNeP treatment decreased VC and transcriptional levels of EZH2. The ex vivo experiments revealed that high Pi stimulation significantly enhanced EZH2 expression and its histone mark, H3K27me3 (methylation of Histone H3 at lysine 27). This epigenetic alteration was accompanied by an elevation in osteogenic markers and a reduction in the expression of VSMC differentiation markers. In vitro, EZH2 and H3K27me3 were noticeably elevated in calcifying VSMCs. Mechanistically, overexpression of EZH2 aggravated the VSMCs\u2019 calcification through upregulation of BMP2. Conclusion: Our study demonstrated the elevated EZH2 expression in calcified vascular tissues from both CKD patients and preclinical models, including CKD mice, cultured rat aortas, and VSMCs calcification models. EZH2 may promote VC through activation of BMP2 signaling. Targeting EZH2 could be a therapeutic strategy against CKD associated VC.<\/jats:p>","DOI":"10.31083\/fbl48723","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:29:27Z","timestamp":1777454967000},"source":"Crossref","is-referenced-by-count":0,"title":["Enhancer of Zeste Homologue 2 Promotes Vascular Calcification Associated With Chronic Kidney Disease"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7685-856X","authenticated-orcid":true,"given":"Pinglan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 201203 Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-3392","authenticated-orcid":true,"given":"Yufeng","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 201203 Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-8766","authenticated-orcid":true,"given":"Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 201203 Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5423-9733","authenticated-orcid":true,"given":"Dongping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 201203 Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1822-9060","authenticated-orcid":true,"given":"Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 201203 Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-2815","authenticated-orcid":true,"given":"Di","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 201203 Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7769-4993","authenticated-orcid":true,"given":"Ayijiaken","family":"Kasimumali","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second People\u2019s Hospital of Kashgar Prefecture, 844000 Kashgar, Xinjiang Uygur Autonomous Region, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0695-385X","authenticated-orcid":true,"given":"Yijing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Jiaxing Hospital of TCM, 314100 Jiaxing, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5390-4626","authenticated-orcid":true,"given":"Chaoyang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, 201203 Shanghai, China"},{"name":"Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 201203 Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Cockwell P, Fisher LA. 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