Inhibition and Role of let-7d in Idiopathic Pulmonary Fibrosis

• DOI: 10.1164/rccm.200911-1698oc
• Publication Date: 2010-04-16T02:40:05Z
• Authors: Kusum V. Pandit; David Corcoran; Hanadie Yousef; Manohar Yarlagadda; Argyris Tzouvelekis; Kevin F. Gibson; Kazuhisa Konishi; Samuel A. Yousem; Mandal Singh; Daniel Handley; Thomas Richards; Moises Selman; Simon C. Watkins; Annie Pardo; Ahmi Ben-Yehudah; Demosthenes Bouros; Oliver Eickelberg; Prabir Ray; Panayiotis V. Benos; Naftali Kaminski
• Keywords: 0303 health sciences; HMGA2 Protein; S100 Proteins; Down-Regulation; Epithelial Cells; Cadherins; Polymerase Chain Reaction; Actins; Idiopathic Pulmonary Fibrosis; 3. Good health; Mice, Inbred C57BL; Pulmonary Alveoli; Mice; MicroRNAs; 03 medical and health sciences; Transforming Growth Factor beta; Animals; Humans; S100 Calcium-Binding Protein A4; Smad3 Protein; Lung; Cells, Cultured; In Situ Hybridization

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually lethal fibrotic lung disease characterized by profound changes in epithelial cell phenotype fibroblast proliferation.To determine expression role of microRNAs IPF.RNA from 10 control IPF tissues was hybridized on Agilent microRNA microarrays results were confirmed quantitative real-time polymerase chain reaction situ hybridization. SMAD3 binding to the let-7d promoter chromatin immunoprecipitation, electrophoretic mobility shift assay, luciferase assays, reduced response transforming growth factor-beta. HMGA2, target, localized immunohistochemistry. In mice, inhibited intratracheal administration antagomir its effects determined immunohistochemistry, immunofluorescence, reaction, morphometry.Eighteen including significantly decreased IPF. Transforming factor-beta down-regulated expression, demonstrated. Inhibition caused increases mesenchymal markers N-cadherin-2, vimentin, alpha-smooth muscle actin (ACTA2) as well HMGA2 multiple lines. lungs number cells expressing correlated with functions. increased alveolar lungs. inhibition vivo septal thickening collagen, ACTA2, S100A4 SFTPC (pulmonary-associated surfactant protein C) cells.Our indicate for The down-regulation profibrotic this vitro suggest key regulatory preventing fibrosis. Clinical trial registered www.clinicaltrials.gov (NCT 00258544).