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Urine-derived exosomes from individuals with IPF carry pro-fibrotic cargo

Sharon Elliot1, Paola Catanuto1, Simone Pereira-Simon1

  • 1DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, United States.

Elife
|December 1, 2022
PubMed
Abstract

Insights

Idiopathic pulmonary fibrosis (IPF) exosomes from urine and lung tissue contain pro-fibrotic microRNAs. These IPF exosomes promote fibrosis in skin and lung models, indicating a systemic disease feature.

Area of Science:

  • Extracellular vesicle biology
  • Pulmonary medicine
  • Fibrosis research

Background:

  • Extracellular vesicles, including exosomes, carry microRNAs (miRNAs) that may serve as disease biomarkers.
  • Idiopathic pulmonary fibrosis (IPF) is associated with altered miRNA expression in lung tissue, sputum, and serum.
  • This study investigates whether exosomes derived from IPF patients' urine and tissues contain pro-fibrotic cargo.

Purpose of the Study:

  • To determine if exosomes from IPF patients' urine and lung tissue promote fibrosis.
  • To analyze the miRNA content of these exosomes.
  • To assess the in vivo and ex vivo effects of these exosomes on fibrotic processes.

Main Methods:

  • Exosomes were isolated from the urine (U-IPFexo) and lung tissue myofibroblasts (MF-IPFexo) of IPF patients, as well as serum from IPF patients and controls.
  • MicroRNA expression profiling of isolated exosomes was performed.
  • In vivo bio-distribution, ex vivo skin wound healing, and in vivo mouse lung models were used to assess exosome effects.

Main Results:

  • U-IPFexo and MF-IPFexo showed specific miRNA expression profiles (miR-let-7d, miR-29a-5p, miR-181b-3p, miR-199a-3p) consistent with IPF.
  • Bioluminescent exosomes were rapidly detected in mouse lungs after intravenous infusion, distributing to other organs.
  • Treatment with U-IPFexo or MF-IPFexo induced a fibrotic phenotype in human/mouse lung punches, ex vivo skin models, and in vivo lung models.

Conclusions:

  • Exosomes from fibrotic sources contain pro-fibrotic miRNAs, suggesting a systemic role in IPF.
  • These IPF-derived exosomes interfere with tissue injury response in lung and skin models.
  • The findings highlight exosomes as a potential factor in the systemic nature of IPF and its progression.
Keywords:
FibrosisUrinecell biologyexosomeshumanmedicinemicroRNAmouse

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