Injured tubular epithelial cells activate fibroblasts to promote kidney fibrosis through miR-150-containing exosomes.

Abstract

The kidney injury induced by ischemia-reperfusion (IR) usually comes with irreversible renal fibrosis, a process that develops into chronic kidney disease (CKD), but the underlying cellular mechanism has yet to be determined. To test our hypothesis that exosomes are tightly connected with kidney fibrosis following AKI, we studied the role of exosomes and the transfer of specific miRNA among other genetic components in injured tubular epithelial cells (TECs). We utilized an experimental IR mice model to simulate the fibrotic environment in injured tissue and detect the production of exosomes, and found that exosome deficiency could significantly alleviate the degree of kidney fibrosis following IR administration. MiRNA profiling of exosomes extracted from renal tissue samples with or without ischemia-reperfusion injury (IRI) revealed that miR-150 was markedly increased as a compelling profibrotic molecule, as evidenced by the fact that overexpression of miR-150 facilitated renal fibrosis. Exosomes isolated from hypoxia TECs also induced the increased production of miR-150. In cocultured fibroblasts with TECs-derived exosomes, we confirmed a direct uptake of exosomal miR-150 by fibroblasts. Finally, we verified that in vivo ischemia mice pretreated with exosomes enriched in miR-150 developed more profibrotic manifestations. Thus, our current study indicated that TECs have the ability to employ exosomes to initiate the activation and proliferation of fibroblasts via direct shuttling of miR-150-containing exosomes during reparative responses, and that exosome/miR-150 provides the groundwork for research to develop more personalized therapeutic approaches for controlling tissue fibrosis.

• Authors: Han Guan, Rui Peng, Likai Mao, Fang Fang, Bin Xu, Ming Chen
• Journal: Experimental cell research (Exp Cell Res) Vol. 392 Issue 2 Pg. 112007 (07 15 2020) ISSN: 1090-2422 [Electronic] United States
• PMID: 32315664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• MicroRNAs
• Mirn150 microRNA, mouse

Topics

• Acute Kidney Injury (complications, pathology)
• Animals
• Cells, Cultured
• Epithelial Cells (metabolism, pathology)
• Exosomes (genetics)
• Fibroblasts (metabolism, pathology)
• Fibrosis (etiology, genetics, pathology)
• Kidney Diseases (etiology, genetics, pathology)
• Kidney Tubules (injuries, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Reperfusion Injury (complications, pathology)