Exosomal miR-17-5p from human embryonic stem cells prevents pulmonary fibrosis by targeting thrombospondin-2.

Abstract

BACKGROUND:

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease characterized by pulmonary fibrosis and lung dysfunction, ultimately leading to respiratory failure. Many preclinical studies have investigated the therapeutic potential of stem cell-derived exosomes in this disease, particularly mesenchymal stem cell-derived exosomes. However, the effects of embryonic stem cell-derived exosomes in IPF remain unclear.

METHODS:

We established a bleomycin (BLM)-induced pulmonary fibrosis mice model and administered human embryonic stem cell exosomes (hESC-exo) from the first day after BLM treatment. The effects of hESC-exo were assessed by pulmonary function tests, biochemical analysis, histochemistry, quantitative real-time polymerase chain reaction (qPCR), and western blot (WB). RNA-seq was used to screen for the potential therapeutic targets of hESC-exo in fibrotic lungs; the identified signaling axis was characterized using a luciferase assay, qPCR, and WB.

RESULTS:

Results indicated hESC-exo administration notably alleviated inflammation, removed deposited collagen, and rescued alveolar architecture in the lungs of BLM-induced mice. In vivo and in vitro tests revealed that hESC-exo-derived miR-17-5p directly bound thrombospondin-2 (Thbs2) to regulate inflammation and fibrosis; thus, hESC-exo protected against BLM toxicity in the lungs via the miR-17-5p/Thbs2 axis.

CONCLUSION:

These results suggest a promising new treatment for fibrosis-associated diseases.

• Authors: Qun Liu, Youkun Bi, Shaole Song, Keqi Zhu, Xinlong Qiao, Huiwen Wang, Guangju Ji
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 14 Issue 1 Pg. 234 (09 04 2023) ISSN: 1757-6512 [Electronic] England
• PMID: 37667335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. BioMed Central Ltd., part of Springer Nature.

Chemical References

• Thrombospondins
• MicroRNAs
• Bleomycin
• MIRN17 microRNA, human

Topics

• Humans
• Animals
• Mice
• Human Embryonic Stem Cells
• Thrombospondins
• MicroRNAs (genetics)
• Idiopathic Pulmonary Fibrosis
• Inflammation
• Bleomycin (toxicity)