{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:22:43Z","timestamp":1789946563908,"version":"4.0.1"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Fund of China","doi-asserted-by":"crossref","award":["81170096\/81573434"],"award-info":[{"award-number":["81170096\/81573434"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Program for New Century Excellent Talents in Heilongjiang Provincial Universities","award":["1252-NCET-013"],"award-info":[{"award-number":["1252-NCET-013"]}]},{"name":"Young Creative Talents Training Program of Heilongjiang Provincial Universities"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Melatonin, a hormone secreted by the pineal gland, possesses multiple biological activities such as antitumor, antioxidant, and anti\u2010ischemia. C\u2010kit<jats:sup>+<\/jats:sup> cardiac progenitor cells (<jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s) have emerged as a promising tool for the treatment of heart diseases. However, the senescence of <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s due to pathological stimuli leads to the decline of <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s' functions and regenerative potential. This study was conducted to demonstrate whether melatonin antagonizes the senescence of <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s in response to oxidative stress. Here, we found that the melatonin treatment markedly inhibited the senescent characteristics of <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s after exposed to sublethal concentration of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, including the increase in senescence\u2010associated <jats:italic>\u03b2<\/jats:italic>\u2010galactosidase (<jats:styled-content style=\"fixed-case\">SA<\/jats:styled-content>\u2010<jats:italic>\u03b2<\/jats:italic>\u2010gal)\u2010positive <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s, senescence\u2010associated heterochromatin loci (<jats:styled-content style=\"fixed-case\">SAHF<\/jats:styled-content>), secretory <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106 level, and the upregulation of p53 and p21 proteins. Senescence\u2010associated proliferation reduction was also attenuated by melatonin in <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s. Luzindole, the melatonin membrane receptor blocker, may block the melatonin\u2010mediated suppression of premature senescence in <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s. Interestingly, we found that long noncoding <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> H19 and its derived miR\u2010675 were downregulated by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s, but melatonin treatment could counter this alteration. Furthermore, knockdown of H19 or miR\u2010675 blocked antisenescence actions of melatonin on H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010treated <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s. It was further verified that H19\u2010derived miR\u2010675 targeted at the 3\u2032<jats:styled-content style=\"fixed-case\">UTR<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">USP<\/jats:styled-content>10, which resulted in the downregulation of p53 and p21 proteins. In summary, melatonin antagonized premature senescence of <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s via H19\/miR\u2010675\/<jats:styled-content style=\"fixed-case\">USP<\/jats:styled-content>10 pathway, which provides new insights into pharmacological actions and potential applications of melatonin on the senescence of <jats:styled-content style=\"fixed-case\">CPC<\/jats:styled-content>s.<\/jats:p>","DOI":"10.1111\/jpi.12331","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T18:01:49Z","timestamp":1460311309000},"page":"82-95","source":"Crossref","is-referenced-by-count":87,"title":["Long noncoding <scp>RNA H<\/scp>19 mediates melatonin inhibition of premature senescence of c\u2010kit<sup>+<\/sup> cardiac progenitor cells by promoting mi<scp>R<\/scp>\u2010675"],"prefix":"10.1111","volume":"61","author":[{"given":"Benzhi","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenya","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongwei","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenbo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (The State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China) Harbin Medical University Harbin China"},{"name":"Department of Pharmacology and Therapeutics Melbourne School of Biomedical Sciences Faculty of Medicine, Dentistry and Health Sciences University of Melbourne Melbourne Vic. 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