Exosomes in pathogenesis, diagnosis, and treatment of pulmonary fibrosis

Abstract

Pulmonary fibrosis (PF) is a group of interstitial lung diseases that seriously endanger human life and health. Despite the current advances in research on the pathogenesis and treatment of PF, the overall quality of survival and survival rates of PF patients remain low, prompting the search for more effective therapeutic approaches. Exosomes are nanoscale vesicles with diameters ranging from approximately 30-150 nm, capable of transporting a variety of molecules in the body and mediating intercellular communication. There is an increasing number of studies focusing on the role of exosomes in PF. This review demonstrates the significance of exosomes in the pathogenesis, diagnosis, and treatment of PF. Exosomes are able to influence inflammatory, immune, and extracellular matrix deposition processes in PF and regulate the corresponding cytokines. Some exosomes detected in sputum, blood, and bronchoalveolar lavage fluid may be used as potential diagnostic and prognostic biomarkers for PF. Exosomes derived from several cells, such as mesenchymal stem cells, have demonstrated potential as PF therapeutic agents. Drug delivery systems using exosomes may also provide new insights into PF therapy.

Keywords: biomarkers; exosomes; pathogenesis; pulmonary fibrosis; therapeutics.

FIGURE 1

Composition of exosome.

FIGURE 2

Biogenesis, secretion and uptake of exosome. Note: ESE, early-sorting endosome; LSE, late-sorting endosome; MVB, multivesicular body; ILV, intraluminal vesicle; ESCRT, endosomal sorting complex required for transport; SNARE, soluble N -ethylmaleimide-sensitive factor attachment protein receptor.

FIGURE 3

Direct effects of regulatory immune cells, fibroblasts and extracellular matrix in pulmonary fibrosis. Note: ECM, extracellular matrix.

FIGURE 4

This figure summarizes the role of regulatory exosomes in PF. Mechanism investigation revealed that exosomes secreted by different kinds of cells, eg: human amnion epithelial cell (HAEC), Menstrual Blood-Derived Endometrial Stem Cell (MenSC), Mesenchymal stem cells (MSC), Human umbilical cord mesenchymal stem cell (HUCMSC), Bone marrow mesenchymal stem cell (BMSC), Pluripotent stem cell (iPSC), Lung spheroid cell(LSC), Vascular endothelial cell (EnC), Macrophage, M2 macrophages. The exosomes transmitted protein cargo and microRNAs regulated MAPK, NF-kb, PI3k/Akt, Wnt/β-catenin, TGFβRI/FoxM1/Smad/β-catenin, HIF-1α/Notch1/PDGFRβ/YAP1/ Twist1 signaling pathways. Finally these pathways assess their interaction with epithelial-mesenchymal transition, apoptosis and proliferation in contradicting findings.