{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:02:33Z","timestamp":1773457353713,"version":"3.50.1"},"reference-count":40,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:p> Hyperphosphatemia, the elevated level of inorganic phosphate (Pi) in serum, is associated with increased cardiovascular morbidities and mortality. The effects of high Pi on endothelial cells are not well studied. This study investigated high Pi-induced endothelial cell apoptosis and the role of microRNA-21. Mouse myocardial endothelial cells (MEC) were cultured in normal (1 mM) and high (5 mM) Pi conditions. Apoptosis was detected by TUNEL staining and flow cytometry. MicroRNA profiles of MEC response to changes in Pi concentration were obtained using gene expression arrays. Expression levels of the microRNA-21 target genes, programmed cell death gene 4 ( PDCD4), poly(ADP-ribose) polymerase ( PARP), and phosphatase and tensin homolog ( PTEN), as well as NF-\u03baB were measured by Western blotting and RT-PCR. MicroRNA-21-specific inhibitors and mimics were used to study effects of microRNA-21 on MEC apoptosis and gene expression regulations. High Pi induced MEC apoptosis and upregulated microRNA-21 expression. MicroRNA-21-specific mimics reproduced high Pi-induced apoptosis in normal Pi medium, and microRNA-21 inhibitors ameliorated the high Pi induction of apoptosis, suggesting that microRNA-21 mediated high Pi-induced MEC apoptosis. The microRNA-21 targets PDCD4, PTEN, PARP, and NF-\u03baB were significantly downregulated in high Pi conditions. High Pi-induced downregulation of PDCD4 was abolished by microRNA-21 inhibitors and selective ERK inhibitor (selumetinib) and was reproduced by microRNA-21 mimics. Inhibitors and mimics of microRNA-21 did not have effects on high Pi-induced NF-\u03baB downregulation. Selumetinib blocked high Pi-induced NF-\u03baB downregulation. MicroRNA-21 mediates high Pi-induced endothelial cell apoptosis, which involves an ERK1\/2\/microRNA-21\/PDCD4 pathway. High Pi-induced downregulation of NF-\u03baB expression is mediated by an ERK1\/2 signaling-dependent but microRNA-21-independent mechanism. <\/jats:p>","DOI":"10.1152\/ajpcell.00198.2018","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T21:09:17Z","timestamp":1537996157000},"page":"C830-C838","source":"Crossref","is-referenced-by-count":12,"title":["MicroRNA-21 mediates high phosphate-induced endothelial cell apoptosis"],"prefix":"10.1152","volume":"315","author":[{"given":"Zhaoyu","family":"Li","sequence":"first","affiliation":[{"name":"Division of Cardiology, McAllister Heart Institute, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina"},{"name":"Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shengyang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szymon","family":"Wiernek","sequence":"additional","affiliation":[{"name":"Division of 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