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MicroRNA-638 inhibits human aortic valve interstitial cell calcification by targeting Sp7

Wenjie Jiao1, Dongyang Zhang1, Dong Wang1

  • 1Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Journal of Cellular and Molecular Medicine
|May 30, 2019
PubMed

Insights

MicroRNA-638 (miR-638) inhibits osteogenic differentiation in human aortic valve interstitial cells (hAVICs) by targeting Sp7. This finding suggests miR-638 as a potential therapeutic target for calcific aortic valve disease (CAVD).

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Gene Regulation

Background:

  • Calcific aortic valve disease (CAVD) is a prevalent condition characterized by pathological changes in heart valves.
  • Osteogenic differentiation of human aortic valve interstitial cells (hAVICs) is a critical process implicated in aortic valve calcification.

Purpose of the Study:

  • To investigate the role and mechanism of microRNA-638 (miR-638) in regulating hAVIC osteogenesis.
  • To explore the potential of miR-638 as a therapeutic target for CAVD.

Main Methods:

  • MiRNA microarray and quantitative real-time PCR (qRT-PCR) to assess miR-638 expression.
  • In vitro experiments involving overexpression and down-regulation of miR-638 in hAVICs.
  • Target prediction analysis and dual-luciferase reporter assays to identify miR-638 targets.
  • Sp7 transcription factor (Sp7) knockdown experiments.

Main Results:

  • miR-638 was significantly upregulated in calcific aortic valves and during hAVIC osteogenic differentiation.
  • Overexpression of miR-638 inhibited hAVIC osteogenesis, while its down-regulation promoted it.
  • Sp7 was confirmed as a direct target of miR-638, and Sp7 knockdown mimicked the inhibitory effects of miR-638 overexpression on hAVIC osteogenesis.

Conclusions:

  • miR-638 exerts an inhibitory effect on hAVIC osteogenic differentiation, potentially through targeting Sp7.
  • These findings highlight miR-638 as a promising therapeutic target for managing CAVD.

Keywords:
Sp7calcific aortic valve diseasehuman aortic valve interstitial cellsmiRNA-638osteogenic differentiation

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