{"title":"<i>MiR-21-5p</i> Promotes Osteogenic Differentiation and Calcification of Valvular Interstitial Cells by Targeting <i>TGFBI</i> in Calcific Aortic Valve Disease.","authors":"Yan Gu, Rongjin Chen, Jianxiang Song, Zhan Shi, Jixiang Wu, Huiwen Chang, Conghu Yuan, Woda Shi, Yajun Zhang","doi":"10.18502/ijph.v53i10.16703","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Calcific aortic valve disease (CAVD) is the most common heart relating disease with high morbidity and mortality, especially in elderly population. While extensive investigations have been devoted to the study of mechanistic pathways related to CAVD, the key factors and mechanisms mediating valve mineralization remain unclear. The aim of this study is to investigate the role of mirnas and their downstream targets in CAVD disease progression. A previous recent multi-omics study suggested a novel CAVD molecular interaction network contained <i>miR-21-5p</i>.</p><p><strong>Methods: </strong>CAV and their pair-matched adjacent normal tissues were obtained from 15 patients pathologically diagnosed as CAVD and admitted in Yancheng Third People's Hospital (The Sixth Affiliated Hospital of Nantong University) from 2019-2021. RT-qPCR was utilized for detection of <i>miR-21-5p</i> and related protein expression levels to confirm the related factors in CAVD progression. Western blotting was applied to strengthen the results of RT-qPCR and confirm osteogenic differentiation of VICs via biomarker detection. The staining of alkaline phosphatase (ALP) and alizarin red was performed to assess the degree of VIC mineralization.</p><p><strong>Results: </strong>We found that <i>miR-21-5p</i> was remarkably increased (<i>P</i><0.0001) in calcified aortic valves (AVs) whereas <i>TGFBI</i> was diminished (<i>P</i><0.01) in CAVD samples compared to the paired normal tissues from CAVD patients. Additionally, <i>TGFBI</i> was targeted by <i>miR-21-5p</i>. Furthermore, overexpressing <i>TGFBI</i> could block VIC osteogenic differentiation mediated by <i>miR-21-5p</i>. To sum up, <i>miR-21-5p</i> promotes VIC osteogenic differentiation and calcification via <i>TGFBI</i> in CAVD progression.</p><p><strong>Conclusion: </strong>Our work might bring a sight on underlying mechanisms of CAVD progression and provide a possible therapeutic target for diagnosis and treatment.</p>","PeriodicalId":49173,"journal":{"name":"Iranian Journal of Public Health","volume":"53 10","pages":"2260-2270"},"PeriodicalIF":1.3000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557769/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Public Health","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.18502/ijph.v53i10.16703","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Calcific aortic valve disease (CAVD) is the most common heart relating disease with high morbidity and mortality, especially in elderly population. While extensive investigations have been devoted to the study of mechanistic pathways related to CAVD, the key factors and mechanisms mediating valve mineralization remain unclear. The aim of this study is to investigate the role of mirnas and their downstream targets in CAVD disease progression. A previous recent multi-omics study suggested a novel CAVD molecular interaction network contained miR-21-5p.
Methods: CAV and their pair-matched adjacent normal tissues were obtained from 15 patients pathologically diagnosed as CAVD and admitted in Yancheng Third People's Hospital (The Sixth Affiliated Hospital of Nantong University) from 2019-2021. RT-qPCR was utilized for detection of miR-21-5p and related protein expression levels to confirm the related factors in CAVD progression. Western blotting was applied to strengthen the results of RT-qPCR and confirm osteogenic differentiation of VICs via biomarker detection. The staining of alkaline phosphatase (ALP) and alizarin red was performed to assess the degree of VIC mineralization.
Results: We found that miR-21-5p was remarkably increased (P<0.0001) in calcified aortic valves (AVs) whereas TGFBI was diminished (P<0.01) in CAVD samples compared to the paired normal tissues from CAVD patients. Additionally, TGFBI was targeted by miR-21-5p. Furthermore, overexpressing TGFBI could block VIC osteogenic differentiation mediated by miR-21-5p. To sum up, miR-21-5p promotes VIC osteogenic differentiation and calcification via TGFBI in CAVD progression.
Conclusion: Our work might bring a sight on underlying mechanisms of CAVD progression and provide a possible therapeutic target for diagnosis and treatment.
期刊介绍：
Iranian Journal of Public Health has been continuously published since 1971, as the only Journal in all health domains, with wide distribution (including WHO in Geneva and Cairo) in two languages (English and Persian). From 2001 issue, the Journal is published only in English language. During the last 41 years more than 2000 scientific research papers, results of health activities, surveys and services, have been published in this Journal. To meet the increasing demand of respected researchers, as of January 2012, the Journal is published monthly. I wish this will assist to promote the level of global knowledge. The main topics that the Journal would welcome are: Bioethics, Disaster and Health, Entomology, Epidemiology, Health and Environment, Health Economics, Health Services, Immunology, Medical Genetics, Mental Health, Microbiology, Nutrition and Food Safety, Occupational Health, Oral Health. We would be very delighted to receive your Original papers, Review Articles, Short communications, Case reports and Scientific Letters to the Editor on the above mentioned research areas.
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