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Publications

Journal Article Epublish

PubMed: 40124162 DOI: 10.1016/j.omtn.2025.102461

Ratio of miRNA-29 to miRNA-199 expression coordinates mesenchymal stem cell repair of bleomycin-induced pulmonary injury.

Mol Ther Nucleic Acids 36(1):102461

Authors: Sharon J Elliot, Dustin Anderson-Terhune, Benjamin Roos, Gustavo A Rubio, Xiaomei Xia, Simone Pereira-Simon, Paola Catanuto, Gina Civettini, Emily S Hagen, Constadina Arvanitis, Shahriar Shahzeidi, Marilyn K Glassberg

Affiliations

  • Stritch School of Medicine, Department of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.
  • Department of Pulmonary and Critical Care, University of Utah, Salt Lake City, UT 84112, USA.
  • Associate Medical Director, Jackson Health System, 1611 NW 12 Avenue, Miami, FL 33136, USA.
  • Department of Medicine, Division of Pulmonary, Critical Care, and Sleep, University of Arizona College of Medicine-Phoenix University Medical Center-Phoenix, Phoenix, AZ 85004, USA.
  • Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
  • Department of Ophthalmology, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
  • Director of Center for Advanced Microscopy & Nikon Imaging Center, Northwestern University, Chicago, IL 60611, USA.
  • Grand Health Institute, 1717 N. Bayshore Drive, Suite R244, Miami, FL 33132, USA.

Abstract

Our previous work demonstrated the anti-fibrotic effects of infusion of adipose-derived mesenchymal stem cells (ASCs) to prevent or repair bleomycin (BLM)-induced lung injury. The present study investigates mechanisms driving these anti-fibrotic effects. Pulmonary fibrosis developed at day 12 in 22-month-old C57BL/6 male mice after intratracheal BLM instillation. There was a decrease in indices of pulmonary fibrosis, including collagen content, AKT activation, collagen types I and III, α-integrin, tumor necrosis factor alpha, and transforming growth factor β mRNA after infusion of ASCs 12 days post-BLM treatment compared to BLM alone. Infusion of ASCs increased the population of alveolar types I and II epithelial cells that had been reduced after BLM treatment. miRNAscope technology and reverse-transcription polymerase chain reaction revealed that ASC-treated mice demonstrated increased miR-29a, decreased miR-199, and increased telomere length, telomerase RNA component, and telomerase reverse transcriptase compared to BLM alone. and experiments using double-transfected mouse or human myofibroblasts (miR-29 mimic, and miR-199 inhibitor) confirmed that alterations of these miRNAs regulate downstream effectors of fibrosis. These data suggest that alteration of the ratio of anti-fibrotic to fibrotic miRNAs and increase in telomere length are critical mechanisms of ASC-mediated repair of BLM-induced pulmonary fibrosis.

MeSH

Cells, Bleomycin, Tumor Necrosis Factor-Alpha, Microscopy, Electron, Scanning Transmission, Fibrosis, Micrornas, Lung Injury, Collagen, Telomerase, Stem Cells, Mesenchymal Stem Cells, Pulmonary Fibrosis, Therapeutics, Telomere