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Cited by 229

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Involvement of MicroRNAs in Hydrogen Peroxide-mediated Gene Regulation and Cellular Injury Response in Vascular Smooth Muscle Cells

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Lin, Ying, Liu, Xiaojun, Cheng, Yunhui, Yang, Jian, Huo, Yuqing, Zhang, Chunxiang·2009·Journal of Biological Chemistry

Abstract

MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate approximately 30% of genes in a cell via degradation or translational inhibition of their target mRNAs. However, the effects of reactive oxygen species (ROS) on miRNA expression and the roles of miRNAs in ROS-mediated gene regulation and biological functions of vascular cells are unclear. Using microarray analysis, we demonstrated that miRNAs are aberrantly expressed in vascular smooth muscle cells (VSMCs) after treatment with hydrogen peroxide (H(2)O(2)). H(2)O(2)-mediated up-regulation of microRNA-21 (miR-21) was further confirmed by quantitative real-time PCR. To determine the potential roles of miRNAs in H(2)O(2)-mediated gene regulation and cellular effects, miR-21 expression was down-regulated by miR-21 inhibitor and up-regulated by pre-miR-21. H(2)O(2)-induced VSMC apoptosis and death were increased by miR-21 inhibitor and decreased by pre-miR-21. Programmed cell death 4(PDCD4) was a direct target of miR-21 that was involved in miR-21-mediated effects on VSMCs. Pre-miR-21-mediated protective effect on VSMC apoptosis and death was blocked via adenovirus-mediated overexpression of PDCD4 without the miR-21 binding site. Moreover, activator protein 1 was a downstream signaling molecule of PDCD4 in miR-21-modulated VSMCs. The results suggest that miRNAs in VSMCs are sensitive to H(2)O(2) stimulation. miRN-21 participates in H(2)O(2)-mediated gene regulation and cellular injury response through PDCD4 and the activator protein 1 pathway. miRNAs might play a role in vascular diseases related to ROS.

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Metadata

Authors
Lin, Y., Liu, X., Cheng, Y., Yang, J., Huo, Y., & Zhang, C.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-03
Volume
284
Issue
12
Pages
7903-7913
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2081069100
Cited by
229
References
9
FWCI
5.54
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Involvement of MicroRNAs in Hydrogen Peroxide-mediated Gene Regulation and Cellular Injury Response in Vascular Smooth Muscle Cells. https://app.cochat.ai/papers/10.1074/jbc.m806920200
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Lin, Y., Liu, X., Cheng, Y., Yang, J., Huo, Y., & Zhang, C. (2009). Involvement of MicroRNAs in Hydrogen Peroxide-mediated Gene Regulation and Cellular Injury Response in Vascular Smooth Muscle Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m806920200

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