{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:22:59Z","timestamp":1784262179623,"version":"3.55.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>Background\/Aims: MicroRNAs play regulatory role in cardiovascular disease. MicroRNA-223 (miR-223) was found to be expressed abundantly in myocardium. TNNI3K, a novel cardiac troponin I (cTnI)-interacting and cardiac hypertrophy related kinase, is computationally predicted as a potential target of miR-223. This study was designed to investigate the cellular and molecular effects of miR-223 on cardiomyoctye hypertrophy, focusing on the role of TNNI3K. Methods: Neonatal rat cardiomyocytes (CMs) were cultured, and CMs hypertrophy was induced by endothelin-1 (ET-1). In vivo cardiac hypertrophy was induced by transverse aorta constriction (TAC) in rats. Expression of miR-223 in CMs and myocardium was detected by real-time PCR (RT-PCR). MiR-223 and TNNI3K were overexpressed in CMs via chemically modifed sense RNA (miR-223 mimic) transfection or recombinant adenovirus infection, respectively. Cell size was measured by surface area calculation using fluorescence microscopy after anti-\u03b1-actinin staining. Expression of hypertrophy-related genes was detected by RT-PCR. The protein expression of TNNI3K and cTnI was determined by Western blots. Luciferase assay was employed to confirm the direct binding of miR-223 to the 3'UTR of TNNI3K mRNA. Intracellular calcium was measured by sensitive fluorescent indicator (Furo-2). Video-based edge detection system was employed to measure cardiomyocyte contractility. Results: MiR-223 was downregulated in ET-1 induced hypertrophic CMs and in hypertrophic myocardium compared with respective controls. MiR-223 overexpression in CMs alleviated ET-1 induced hypertrophy, evidenced by smaller cell surface area and downregulated ANP, \u03b1-actinin, Myh6 and Myh7 expression. Luciferase reporter gene assay showed that TNNI3K serves as a direct target gene of miR-223. In miR-223-overexpressed CMs, the protein expression of TNNI3K was significantly downregulated. MiR-223 overexpression also rescued the upregulated TNNI3K expression in hypertrophic CMs. Furthermore, cTnI phosphorylation was downregulated post miR-223 overexpression. Ad.rTNNI3K increased intracellular Ca2+ concentrations and cell shortening in CMs, while miR-223 overexpression significantly rescued these hypertrophic effects. Conclusion: By direct targeting TNNI3K, miR-223 could suppress CMs hypertrophy via downregulating cTnI phosphorylation, reducing intracellular Ca2+ and contractility of CMs. miR-223 \/ TNNI3K axis may thus be major players of CMs hypertrophy.<\/jats:p>","DOI":"10.1159\/000373970","type":"journal-article","created":{"date-parts":[[2015,3,23]],"date-time":"2015-03-23T09:04:17Z","timestamp":1427101457000},"page":"1546-1556","source":"Crossref","is-referenced-by-count":48,"title":["MicroRNA-223 Displays a Protective Role Against Cardiomyocyte Hypertrophy by Targeting Cardiac Troponin I-Interacting Kinase"],"prefix":"10.1159","volume":"35","author":[{"given":"Yao-Sheng","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Shu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Gang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2015,3,12]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/373970","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/373970","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:37:18Z","timestamp":1745429838000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000373970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,3,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000373970","archive":["Portico"],"relation":{},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015]]}}}