{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T18:08:27Z","timestamp":1785262107497,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T00:00:00Z","timestamp":1740873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T00:00:00Z","timestamp":1740873600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060053"],"award-info":[{"award-number":["82060053"]}],"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":["82260083"],"award-info":[{"award-number":["82260083"]}],"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":["82170440"],"award-info":[{"award-number":["82170440"]}],"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":["U220A20270"],"award-info":[{"award-number":["U220A20270"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013142","name":"Key Research and Development Project of Hainan Province","doi-asserted-by":"publisher","award":["ZDYF2022SHFZ038"],"award-info":[{"award-number":["ZDYF2022SHFZ038"]}],"id":[{"id":"10.13039\/501100013142","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013142","name":"Key Research and Development Project of Hainan Province","doi-asserted-by":"publisher","award":["ZDYF2020122"],"award-info":[{"award-number":["ZDYF2020122"]}],"id":[{"id":"10.13039\/501100013142","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rnd3 is a small Rho\u2010GTPase that has been implicated in various cardiovascular diseases. Yet, its role in diabetes\u2010induced cardiomyocyte senescence remains unknown. Here we tested the role of Rnd3 in cardiomyocyte senescence and diabetic cardiomyopathy (DCM). The expression of\n                    <jats:italic>Rnd3<\/jats:italic>\n                    was found to be reduced in peripheral blood mononuclear cells from diabetic patients and correlated negatively with age but positively with cardiac function. In 96\u2010week\u2010old Sprague Dawley (SD) rats, cardiac function was impaired, accompanied by an increased number of SA\u2010\u03b2\u2010gal\u2010positive cells and elevated levels of the senescence\u2010associated secretory phenotype (SASP) related factors, compared to those of 12\u2010week\u2010old rats. Diabetes and high glucose (HG, 35\u2009mmol\/L D\u2010glucose) suppressed\n                    <jats:italic>Rnd3<\/jats:italic>\n                    expression in cardiomyocytes and induced cardiomyocyte senescence. The deficiency of\n                    <jats:italic>Rnd3<\/jats:italic>\n                    exacerbated cardiomyocyte senescence in\u00a0vitro and in\u00a0vivo. MicroRNA sequencing in AC16 cells identified a conserved miR\u2010103a\u20103p (present in humans and rats) as a key HG\u2010upregulated microRNA that bound to the\n                    <jats:italic>Rnd3<\/jats:italic>\n                    3\u2032\u2010UTR. In cultured cardiomyocytes, miR\u2010103a\u20103p inhibitors antagonized HG\u2010induced cardiomyocyte senescence dependent on\n                    <jats:italic>Rnd3<\/jats:italic>\n                    expression. Treatment with AAV9 vectors carrying miR\u2010103a\u20103p sponges and\n                    <jats:italic>Rnd3<\/jats:italic>\n                    \u2010overexpressing plasmids alleviated cardiomyocyte senescence and restored cardiac function in diabetic SD rats. HG stimulation increased STAT3 (Tyr705) phosphorylation and promoted its nuclear translocation in H9C2 cells, an effect exacerbated by\n                    <jats:italic>Rnd3<\/jats:italic>\n                    knockout. Mechanistically, Rnd3 interacted with p\u2010STAT3 in the cytoplasm, facilitating proteasome\u2010mediated ubiquitination and p\u2010STAT3 degradation. The STAT3 inhibitor S3I\u2010201 blocked HG\u2010induced STAT3 activation and mitigated cardiomyocyte senescence. These findings suggest that diabetes induces cardiomyocyte senescence via the miR\u2010103a\u20103p\/Rnd3\/STAT3 signaling pathway, highlighting a potential therapeutic target for DCM.\n                  <\/jats:p>","DOI":"10.1111\/acel.70031","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T02:53:27Z","timestamp":1740970407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Diabetes Advances Cardiomyocyte Senescence Through Interfering\n                    <i>Rnd3<\/i>\n                    Expression and Function"],"prefix":"10.1111","volume":"24","author":[{"given":"Linxu","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"},{"name":"Public Research Center of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingci","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, School of Basic Medicine Sciences Guangdong Medical University  Zhanjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijia","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxuan","family":"Chai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebin","family":"Ling","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"},{"name":"Department of Cardiovascular Medicine The First Affiliated Hospital of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Public Research Center of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-8873","authenticated-orcid":false,"given":"Zhihua","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, School of Basic Medicine Sciences Guangdong Medical University  Zhanjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1869-1458","authenticated-orcid":false,"given":"Wei","family":"Jie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"},{"name":"Department of Cardiovascular Medicine The First Affiliated Hospital of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9740-9819","authenticated-orcid":false,"given":"Junli","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education &amp; Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health Hainan Medical University  Haikou China"},{"name":"Department of Cardiovascular Medicine The First Affiliated Hospital of Hainan Medical University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010023\u201000881\u20103"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056589"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-S011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.343129.120"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427\u2010022\u20102161\u20103"},{"key":"e_1_2_9_7_1","first-page":"101","article-title":"Trends in Aging\u2014United States and Worldwide","volume":"52","author":"Centers for Disease Control and Prevention","year":"2003","journal-title":"MMWR. Morbidity and Mortality Weekly Report"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1788"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab161"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.033700"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16\u20102016"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101338"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010publhealth\u2010052620\u2010091107"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00730.2014"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010024\u201007322\u20100"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006373\u20101"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3838"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu034"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1199"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2024.5373"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154910"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311586"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201019\u20100334"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c150018"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101610"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.12267"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315889"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219995110"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201011515\u2010z"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569\u2010021\u201000624\u20102"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.246876"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0115"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2020.4661"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609757104"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101813"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.08.002"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010020\u201001705\u20109"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00280"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010016\u20100292\u20104"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122701"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102204"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658\u2010022\u201000388\u20108"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.4248\/BR201304007"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010021\u201000689\u20102"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304940"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108779"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06412"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.235"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2019.4128"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.77043"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1406"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.042"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308688"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105197"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010022\u201005809\u2010z"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70031","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70031","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:09:54Z","timestamp":1781132994000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,2]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/acel.70031"],"URL":"https:\/\/doi.org\/10.1111\/acel.70031","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,2]]},"assertion":[{"value":"2024-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70031"}}