Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts

MicroRNAs are small noncoding RNAs that inhibit protein expression. We have previously shown that the inhibition of the microRNA let-7d in epithelial cells caused changes consistent with epithelial-to-mesenchymal transition (EMT) both in vitro and in vivo. The aim of this study was to determine whet...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2014-03, Vol.306 (6), p.L534-L542
Main Authors: Huleihel, Luai, Ben-Yehudah, Ahmi, Milosevic, Jadranka, Yu, Guoying, Pandit, Kusum, Sakamoto, Koji, Yousef, Hanadie, LeJeune, Megan, Coon, Tiffany A, Redinger, Carrie J, Chensny, Lara, Manor, Ester, Schatten, Gerald, Kaminski, Naftali
Format: Article
Language:English
Subjects:
Actins - metabolism
Cadherins - metabolism
Calcium-Binding Proteins - metabolism
Cell Movement - genetics
Cell Proliferation
Cells
Cells, Cultured
Epithelial-Mesenchymal Transition
Fibroblasts - cytology
Fibroblasts - metabolism
Fibronectins - metabolism
Genotype & phenotype
HMGA2 Protein - metabolism
HMGB2 Protein - metabolism
Humans
Idiopathic Pulmonary Fibrosis - metabolism
Idiopathic Pulmonary Fibrosis - pathology
Keratin-19 - metabolism
Lung - cytology
Lung - metabolism
MicroRNAs - genetics
Myofibroblasts - metabolism
Protein expression
Pulmonary Alveoli - metabolism
Pulmonary Fibrosis - genetics
Pulmonary Fibrosis - metabolism
Ribonucleic acid
RNA
Snail Family Transcription Factors
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
Transforming Growth Factor beta - metabolism
Wound healing
Wound Healing - genetics
Zonula Occludens-1 Protein - metabolism
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Summary:MicroRNAs are small noncoding RNAs that inhibit protein expression. We have previously shown that the inhibition of the microRNA let-7d in epithelial cells caused changes consistent with epithelial-to-mesenchymal transition (EMT) both in vitro and in vivo. The aim of this study was to determine whether the introduction of let-7d into fibroblasts alters their mesenchymal properties. Transfection of primary fibroblasts with let-7d caused a decrease in expression of the mesenchymal markers α-smooth muscle actin, N-cadherin, fibroblast-specific protein-1, and fibronectin, as well as an increase in the epithelial markers tight junction protein-1 and keratin 19. Phenotypic changes were also present, including a delay in wound healing, reduced motility, and proliferation of fibroblasts following transfection. In addition, we examined the effects of transfection on fibroblast responsiveness to TGF-β, an important factor in many fibrotic processes such as lung fibrosis and found that let-7d transfection significantly attenuated high-mobility group-A2 protein induction by TGF-β. Our results indicate that administration of the epithelial microRNA let-7d can significantly alter the phenotype of primary fibroblasts.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00149.2013