{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:30:49Z","timestamp":1787610649717,"version":"build-2736575974"},"reference-count":26,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400178"],"award-info":[{"award-number":["81400178"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900216"],"award-info":[{"award-number":["81900216"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["BK20160231"],"award-info":[{"award-number":["BK20160231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["BK20140226"],"award-info":[{"award-number":["BK20140226"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["KC21067"],"award-info":[{"award-number":["KC21067"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["KC21171"],"award-info":[{"award-number":["KC21171"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["81400178"],"award-info":[{"award-number":["81400178"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["81900216"],"award-info":[{"award-number":["81900216"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20160231"],"award-info":[{"award-number":["BK20160231"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20140226"],"award-info":[{"award-number":["BK20140226"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["KC21067"],"award-info":[{"award-number":["KC21067"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["KC21171"],"award-info":[{"award-number":["KC21171"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Program of Xuzhou","award":["81400178"],"award-info":[{"award-number":["81400178"]}]},{"name":"Science and Technology Program of Xuzhou","award":["81900216"],"award-info":[{"award-number":["81900216"]}]},{"name":"Science and Technology Program of Xuzhou","award":["BK20160231"],"award-info":[{"award-number":["BK20160231"]}]},{"name":"Science and Technology Program of Xuzhou","award":["BK20140226"],"award-info":[{"award-number":["BK20140226"]}]},{"name":"Science and Technology Program of Xuzhou","award":["KC21067"],"award-info":[{"award-number":["KC21067"]}]},{"name":"Science and Technology Program of Xuzhou","award":["KC21171"],"award-info":[{"award-number":["KC21171"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aims: Kr\u00fcppel-like Factor 9 (KLF9) is a transcription factor that regulates multiple disease processes. Studies have focused on the role of KLF9 in the redox system. In this study, we aimed to explore the effect of KLF9 on diabetic cardiomyopathy. Methods and Results: Cardiac-specific overexpression or silencing of KLF9 in C57BL\/6 J mice was induced with an adeno-associated virus 9 (AAV9) delivery system. Mice were also subjected to streptozotocin injection to establish a diabetic cardiomyopathy model. In addition, neonatal rat cardiomyocytes were used to assess the possible role of KLF9 in vitro by incubation with KLF9 adenovirus or small interfering RNA against KLF9. To clarify the involvement of peroxisome proliferator-activated receptors (PPAR\u03b3), mice were subjected to GW9662 injection to inhibit PPAR\u03b3. KLF9 was upregulated in the hearts of mice with diabetic cardiomyopathy and in cardiomyocytes. In addition, KLF9 overexpression in the heart deteriorated cardiac function and aggravated hypertrophic fibrosis, the inflammatory response and oxidative stress in mice with diabetic cardiomyopathy. Conversely, cardiac-specific silencing of KLF9 ameliorated cardiac dysfunction and alleviated hypertrophy, fibrosis, the cardiac inflammatory response and oxidative stress. In vitro, KLF9 silencing in cardiomyocytes enhanced inflammatory cytokine release and oxidative stress; KLF9 overexpression increased these detrimental responses. Moreover, KLF9 was found to regulate the transcription of PPAR\u03b3, which suppressed the expression and nuclear translocation of nuclear Factor E2-related Factor 2 (NRF2). In mice injected with a PPAR\u03b3 inhibitor, the protective effects of KLF9 knockdown on diabetic cardiomyopathy were counteracted by GW9662 injection. Conclusions: KLF9 aggravates cardiac dysfunction, the inflammatory response and oxidative stress in mice with diabetic cardiomyopathy. KLF9 may become a therapeutic target for diabetic cardiomyopathy.<\/jats:p>","DOI":"10.3390\/cells11213393","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T20:37:58Z","timestamp":1666903078000},"page":"3393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["KLF9 Aggravates Streptozotocin-Induced Diabetic Cardiomyopathy by Inhibiting PPAR\u03b3\/NRF2 Signalling"],"prefix":"10.3390","volume":"11","author":[{"given":"Fangfang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfeng","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunrui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, China"},{"name":"Institute 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