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

DOI Web Site 2 Citations
  • Luai Huleihel
    Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut;
  • Ahmi Ben-Yehudah
    Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh Development Center, Magee-Women's Research Institute and Foundation, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and
  • Jadranka Milosevic
    University of Pittsburgh School of Medicine, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine,
  • Guoying Yu
    Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut;
  • Kusum Pandit
    University of Pittsburgh School of Medicine, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine,
  • Koji Sakamoto
    Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut;
  • Hanadie Yousef
    University of Pittsburgh School of Medicine, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine,
  • Megan LeJeune
    University of Pittsburgh School of Medicine, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine,
  • Tiffany A. Coon
    Department of Medicine, University of Pittsburgh, Pittsburgh;
  • Carrie J. Redinger
    Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh Development Center, Magee-Women's Research Institute and Foundation, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and
  • Lara Chensny
    University of Pittsburgh School of Medicine, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Pulmonary, Allergy, and Critical Care Medicine,
  • Ester Manor
    Department Of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel
  • Gerald Schatten
    Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh Development Center, Magee-Women's Research Institute and Foundation, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and
  • Naftali Kaminski
    Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut;

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<jats:p>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.</jats:p>

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