Exosomes from tubular epithelial cells undergoing epithelial-to-mesenchymal transition promote renal fibrosis by M1 macrophage activation.
epithelial‐to‐mesenchymal transition
exosomes
kidney fibrosis
macrophage
tubular epithelial cells
Journal
FASEB bioAdvances
ISSN: 2573-9832
Titre abrégé: FASEB Bioadv
Pays: United States
ID NLM: 101733210
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
received:
13
07
2022
revised:
20
11
2022
accepted:
09
01
2023
entrez:
6
3
2023
pubmed:
7
3
2023
medline:
7
3
2023
Statut:
epublish
Résumé
Kidney fibrosis is the common final pathway of chronic kidney disease (CKD), and it is distinguished by inflammation, mesenchymal transition with myofibroblast formation, and epithelial-to-mesenchymal transition (EMT). Macrophages are protuberant inflammatory cells in the kidney, and their roles are dependent on their phenotypes. However, it remains unclear whether tubular epithelial cells (TECs) undergoing EMT can influence the phenotypes of macrophages and the underlying mechanisms during the development of kidney fibrosis. Here, we investigated the characteristics of TECs and macrophages during kidney fibrosis with a focus on EMT and inflammation. We found that the coculture of exosomes from transforming growth factor-beta (TGF-β)-induced TECs with macrophages induced macrophage M1 polarization, while exosomes from TECs without TGF-β stimulation or stimulation with TGF-β alone did not induce an increase in M1 macrophage-related markers. Notably, TECs induced to undergo EMT by TGF-β treatment released more exosomes than the other groups. Furthermore, it is noteworthy that when we injected exosomes from TECs undergoing EMT into mice, in addition to the high level of inflammatory response and the activation of M1 macrophages, the indicators of EMT and renal fibrosis in mouse kidney tissue were correspondingly elevated. In summary, exosomes from TECs undergoing EMT by TGF-β treatment induced M1 polarization and led to a positive feedback effect for further EMT and the development of renal fibrosis. Therefore, the obstacle to the release of such exosomes may be a novel therapeutic strategy for CKD.
Identifiants
pubmed: 36876297
doi: 10.1096/fba.2022-00080
pii: FBA21363
pmc: PMC9983075
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101-113Informations de copyright
©2023 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.
Déclaration de conflit d'intérêts
The authors affirm that the research was directed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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