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Published in:

01-04-2012 | Original Paper

MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4

Authors: Zhen Liu, Cui-Ling Lu, Li-Ping Cui, Yong-Liang Hu, Qi Yu, Ying Jiang, Tian Ma, Da-Kai Jiao, Di Wang, Chi-Yu Jia

Published in: Archives of Dermatological Research | Issue 3/2012

Abstract

During wound healing and tissue repair the dermal fibroblast-to-myofibroblast transdifferentiation plays an important role, transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor of transdifferentiation. MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators of gene expression. The involvement of miRNAs and their roles in TGF-β1-induced myofibroblast transdifferentiation remains to be determined in detail. The current study found that the expression of miR-146a was upregulated in human dermal fibroblasts cells in response to TGF-β1 stimulation in dose-dependent manner by quantitative RT-PCR. Bioinformatic analyses predict that signaling effectors mothers against decapentaplegic protein 4 (SMAD4) is a miR-146a target gene. Luciferase assay demonstrated that miR-146a mimics suppressed SMAD4 3′-UTR reporter construct activity. Furthermore, miR-146a overexpression in dermal fibroblast did not decrease target mRNA levels, but significantly reduced target protein expression. In addition, dermal fibroblasts transfected with miR-146a mimics exhibited attenuated TGF-β1 -induced α-smooth muscle actin (α-SMA) expression compared with the control. This study demonstrated that miR-146a may function as a novel negative regulator to modulate myofibroblast transdifferentiation during TGF-β1 induction by targeting SMAD4.

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Title: MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4
Authors: Zhen Liu
Cui-Ling Lu
Li-Ping Cui
Yong-Liang Hu
Qi Yu
Ying Jiang
Tian Ma
Da-Kai Jiao
Di Wang
Chi-Yu Jia
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: Archives of Dermatological Research / Issue 3/2012
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-011-1178-0

At a glance: The STEP trials

Springer Medicine

MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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