{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:06:15Z","timestamp":1793498775325,"version":"4.5.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370406"],"award-info":[{"award-number":["82370406"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To exam the role of miR\u201092a\/KLF2\/miR\u2010483 in the pathogenesis of metabolic syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, the serum of healthy controls and patients with metabolic syndrome were collected to detect the circulating level of miR\u201092a and miR\u2010483. In vitro cultured HUVECs, overexpression or suppression of miR\u201092a, miR\u2010483 or KLF2 to determine the relationship among miR\u201092a, KLF2 and miR\u2010483. Ang II, ox\u2010LDL, or high glucose treatment were used to mimic the metabolic syndrome. HUVECs or HepG2 cells were treated with Telmisartan, Atorvastatin, or metformin, the miR\u2010483 and its target gene expression was detected. In animal experiment, ob\/ob mice were chose to confirm the changes of miR\u201092a, KLF2, and miR\u2010483.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the healthy controls, the level of miR\u201092a was significantly increased, while miR\u2010483 level was remarkably decreased in the patients with metabolic syndrome. In vitro cultured HUVECS, overexpression of miR\u201092a significantly reduced the expression of miR\u2010483, but overexpression of miR\u2010483 had no effect on miR\u201092a. Overexpression of KLF2 could downregulate miR\u2010483 level, while inhibition of KLF2 had the opposite effect. When HUVECs and HepG2 were stimulated with Ang II, ox\u2010LDL and high glucose, the expression of miR\u2010483 was significantly decreased and its target genes was increased. Anti\u2010miR\u201092a could reverse the effect. Furthermore, Telmisartan, Atorvastatin, and Metformin significantly increased miR\u2010483 expression and decreased its target gene expression, which could be reversed by miR\u201092a mimic. The level of miR\u201092a was significantly increased in HepG2 cells, which were treated with exosomes derived from endothelial cells with miR\u201092a overexpression. ob\/ob mice showed the similar effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Endothelial dysfunction and fatty liver are critically involved in the pathogenesis of metabolic syndrome. MicroRNAs can mediate the cellular communication between vascular endothelial cells (ECs) and distal cell. Serum miR\u201092a level was higher in metabolic syndrome patients than controls. KLF2 is the target gene of miR\u201092a, which can increase the production of miR\u2010483, miR\u2010483 acts on its target genes CTGF, ET\u20101, and \u03b2\u2010catenin to protect cell function. EC miR\u201092a is secreted out of cells into the blood, circulates through the blood to the liver, and continues to exert its biological effects after being absorbed by hepatocytes. LNA\u2010miR\u201092a administration reversed endothelial cell damage and fatty liver caused by metabolic syndrome by affecting the KLF2\/miR\u2010483 pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.14416","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T10:25:57Z","timestamp":1738405557000},"page":"893-906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>miR<\/scp>\u201092a aggravates metabolic syndrome via <scp>KLF2<\/scp>\/<scp>miR<\/scp>\u2010483 axis"],"prefix":"10.1111","volume":"16","author":[{"given":"Zhe","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Public Health, Health Science Center Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Shaanxi Blood Center  Xi'an Shaanxi 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