Novel insight into the protective role of exosomes in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease of which the etiology is not well understood. It is characterized by the progressive and irreversible destruction of the lung architecture caused by the formation of a fibrotic scar tissue leading to a progressive degradation of lung function.

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or several years now, the Molecular Angiogenesis (Ingrid Struman) and Pulmonology (Makon-Sébastien Njock et Julien Guiot) laboratories have initiated a collaboration aimed at determining the role of exosomes in this pathology. Exosomes are small extracellular vesicles about 100 nm in size and secreted by cells. These vesicles play a role in the communication between cells and allow the exchange of proteins or genetic material. Together, this team showed two years ago that exosomes can be isolated from sputum samples from patients with IPF and contain microRNAs that could serve as disease biomarkers (Njock, Guiot et al., (2018), Thorax). Following this, the teams focused more specifically on one of them: the miR-142-3P. This study has just been published in the journal Thorax (Guiot et al., (2020), Thorax). The researchers show that analysis of cells isolated from the sputum of patients shows a strong correlation of miR-142-3P with macrophages, suggesting that the latter are responsible for the high level of this microRNA. The microRNA targets the TGF-B pathway, and can thus impact the expression of pro-fibrotic genes. The exosomes released by the macrophages can therefore, by delivering the anti-fibrotic miR-142-3P to the alveolar epithelial cells and to the fibroblasts, affect their proliferation and reduce fibrosis.

These results suggest that macrophage-derived exosomes may fight against fibrosis in patients with IPF.
The current work of the 2 laboratories aims to determine whether exosomes can be used as vectors to deliver anti-fibrotic microRNA and thus this work revealed a new therapeutic potential to treat pulmonary fibrotic disease.
This close collaboration between the two laboratories allows an efficient approach of questions arising directly from the clinical evaluation of patients towards targeted translational research.

Teams

Laboratory of Molecular Angiogenesis - GIGA-Cancer

Ingrid Struman – i.struman@uliege.be

Laboratory of Pneumology - GIGA I3

Julien Guiot – jguiot@uliege.be

Makon-Sébastien Njock – ms.njock@chuliege.be

References

Guiot, J., Cambier, M., Boeckx, A., Henket, M., Nivelles, O., Gester, F., Louis, E., Malaise, M., Dequiedt, F., Louis, R., Struman, I., and Njock, M.-S. (2020). Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p. Thorax thoraxjnl-2019-214077.

Njock, M.S., Guiot, J., Henket, M.A., Nivelles, O., Thiry, M., Dequiedt, F., Corhay, J.L., Louis, R.E., and Struman, I. (2018). Sputum exosomes: Promising biomarkers for idiopathic pulmonary fibrosis. Thorax 74, 309–312.