Inhibition of miR-101-3p prevents human aortic valve interstitial cell calcification through regulation of CDH11/SOX9 expression.
Inhibition of miR-101-3p prevents human aortic valve interstitial cell calcification through regulation of CDH11/SOX9 expression.
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DOI：
10.1186/s10020-023-00619-4
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发表时间：
2023-02-21
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影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
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钙化性主动脉瓣疾病（CAVD）是成人心脏病的第二大原因。本研究的目的是探讨miR-101-3p是否在人主动脉瓣间质细胞（HAVICs）钙化中发挥作用及其潜在机制。使用小 RNA 深度测序和 qPCR 分析来确定钙化的人主动脉瓣中 microRNA 表达的变化。数据显示，钙化的人主动脉瓣中 miR-101-3p 水平升高。使用培养的原代HAVIC，我们证明在用成骨条件培养基处理的HAVIC中，miR-101-3p模拟物促进钙化并上调成骨途径，而抗miR-101-3p抑制成骨分化并防止钙化。从机制上讲，miR-101-3p直接靶向钙粘蛋白11（CDH11）和Sry相关的高迁移率族蛋白9（SOX9），它们是软骨形成和成骨调节的关键因素。 CDH11 和 SOX9 表达在钙化的人 HAVIC 中均下调。抑制 miR-101-3p 可恢复 CDH11、SOX9 和 ASPN 的表达，并阻止钙化条件下 HAVIC 的成骨。 miR-101-3p 通过调节 CDH11/SOX9 表达在 HAVIC 钙化中发挥重要作用。这一发现很重要，因为它揭示了 miR-1013p 可能是钙化性主动脉瓣疾病的潜在治疗靶点。在线版本包含可在 10.1186/s10020-023-00619-4 获取的补充材料。
Calcific aortic valve disease (CAVD) is the second leading cause of adult heart diseases. The purpose of this study is to investigate whether miR-101-3p plays a role in the human aortic valve interstitial cells (HAVICs) calcification and the underlying mechanisms. Small RNA deep sequencing and qPCR analysis were used to determine changes in microRNA expression in calcified human aortic valves. The data showed that miR-101-3p levels were increased in the calcified human aortic valves. Using cultured primary HAVICs, we demonstrated that the miR-101-3p mimic promoted calcification and upregulated the osteogenesis pathway, while anti-miR-101-3p inhibited osteogenic differentiation and prevented calcification in HAVICs treated with the osteogenic conditioned medium. Mechanistically, miR-101-3p directly targeted cadherin-11 (CDH11) and Sry-related high-mobility-group box 9 (SOX9), key factors in the regulation of chondrogenesis and osteogenesis. Both CDH11 and SOX9 expressions were downregulated in the calcified human HAVICs. Inhibition of miR-101-3p restored expression of CDH11, SOX9 and ASPN and prevented osteogenesis in HAVICs under the calcific condition. miR-101-3p plays an important role in HAVIC calcification through regulation of CDH11/SOX9 expression. The finding is important as it reveals that miR-1013p may be a potential therapeutic target for calcific aortic valve disease. The online version contains supplementary material available at 10.1186/s10020-023-00619-4.
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影响因子：
3.1
作者：
Bruderer, M.;Richards, R. G.;Stoddart, M. J.
通讯作者：
Stoddart, M. J.
DOI：
10.1002/jbmr.2287
发表时间：
2014-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Chen H;Ghori-Javed FY;Rashid H;Adhami MD;Serra R;Gutierrez SE;Javed A
通讯作者：
Javed A
影响因子：
20.1
作者：
Chen K;Wang S;Sun QW;Zhang B;Ullah M;Sun Z
通讯作者：
Sun Z
影响因子：
7.8
作者：
Chen J;Lin Y;Sun Z
通讯作者：
Sun Z
影响因子：
158.5
作者：
Cowell, SJ;Newby, DE;Boon, NA
通讯作者：
Boon, NA