MicroRNA-212-5p, an anti-proliferative miRNA, attenuates hypoxia and sugen/hypoxia-induced pulmonary hypertension in rodents

Tianji Chen; Miranda R. Sun; Qiyuan Zhou; Alyssa M. Guzman; Ramaswamy Ramchandran; Jiwang Chen; Dustin R. Fraidenburg; Balaji Ganesh; Mark Maienschein-Cline; Karl Obrietan; J. Usha Raj

Molecular Therapy: Nucleic Acids (Sep 2022)

MicroRNA-212-5p, an anti-proliferative miRNA, attenuates hypoxia and sugen/hypoxia-induced pulmonary hypertension in rodents

Tianji Chen,
Miranda R. Sun,
Qiyuan Zhou,
Alyssa M. Guzman,
Ramaswamy Ramchandran,
Jiwang Chen,
Dustin R. Fraidenburg,
Balaji Ganesh,
Mark Maienschein-Cline,
Karl Obrietan,
J. Usha Raj

Affiliations

Tianji Chen: Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Corresponding author Tianji Chen, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Miranda R. Sun: Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Qiyuan Zhou: Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Alyssa M. Guzman: Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Ramaswamy Ramchandran: Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Jiwang Chen: Cardiovascular Research Center, University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, Chicago, IL 60612, USA
Dustin R. Fraidenburg: Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, Chicago, IL 60612, USA
Balaji Ganesh: Flow Cytometry Core, University of Illinois at Chicago, Chicago, IL 60612, USA
Mark Maienschein-Cline: Research Informatics Core, University of Illinois at Chicago, Chicago, IL 60612, USA
Karl Obrietan: Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA
J. Usha Raj: Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Corresponding author J Usha Raj, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.

Journal volume & issue: Vol. 29
pp. 204 – 216

Abstract

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MicroRNAs (miRNA, miR-) play important roles in disease development. In this study, we identified an anti-proliferative miRNA, miR-212-5p, that is induced in pulmonary artery smooth muscle cells (PASMCs) and lungs of pulmonary hypertension (PH) patients and rodents with experimental PH. We found that smooth muscle cell (SMC)-specific knockout of miR-212-5p exacerbated hypoxia-induced pulmonary vascular remodeling and PH in mice, suggesting that miR-212-5p may be upregulated in PASMCs to act as an endogenous inhibitor of PH, possibly by suppressing PASMC proliferation. Extracellular vesicles (EVs) have been shown recently to be promising drug delivery tools for disease treatment. We generated endothelium-derived EVs with an enriched miR-212-5p load, 212-eEVs, and found that they significantly attenuated hypoxia-induced PH in mice and Sugen/hypoxia-induced severe PH in rats, providing proof of concept that engineered endothelium-derived EVs can be used to deliver miRNA into lungs for treatment of severe PH.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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