Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts
| Autor: | Kusum Pandit, Megan LeJeune, Hanadie Yousef, Koji Sakamoto, Carrie J. Redinger, Lara Chensny, Tiffany A. Coon, Ester Manor, Jadranka Milosevic, Luai Huleihel, Ahmi Ben-Yehudah, Guoying Yu, Gerald Schatten, Naftali Kaminski |
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| Rok vydání: | 2014 |
| Předmět: |
Pulmonary and Respiratory Medicine
Epithelial-Mesenchymal Transition Physiology Pulmonary Fibrosis Biology Transfection Cell Movement Transforming Growth Factor beta Physiology (medical) microRNA medicine HMGB2 Protein Humans S100 Calcium-Binding Protein A4 Epithelial–mesenchymal transition Myofibroblasts Fibroblast Lung Cells Cultured Cell Proliferation Keratin-19 Wound Healing Calcium-Binding Proteins HMGA2 Protein Mesenchymal stem cell Articles Cell Biology Fibroblasts Cadherins Actins Idiopathic Pulmonary Fibrosis Fibronectins Cell biology Pulmonary Alveoli Fibronectin MicroRNAs medicine.anatomical_structure Zonula Occludens-1 Protein biology.protein Snail Family Transcription Factors Wound healing Myofibroblast Transcription Factors |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 306:L534-L542 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00149.2013 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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