Macrophage-derived, LRG1-enriched extracellular vesicles exacerbate aristolochic acid nephropathy in a TGFßR1-dependent manner.
Cell Biol Toxicol
; 38(4): 629-648, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-34677723
Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by some herbal medicines, but treatment remains ineffective. We previously found that leucine-rich α-2-glycoprotein 1 (LRG1), which regulates cellular processes, plays an important role in a kidney injury model. However, the underlying mechanism by which LRG1 regulates AAN is still unknown. In this study, we established an AAN model in vivo, a coculture system of macrophages and TECs, and a macrophage/TEC conditioned media culture model in vitro. We found that macrophage infiltration promoted injury, oxidative stress, and apoptosis in TECs. Furthermore, the role of macrophages in AAN was dependent on macrophage-derived extracellular vesicles (EVs). Importantly, we found that macrophage-derived, LRG1-enriched EVs induced TEC injury and apoptosis via a TGFßR1-dependent process. This study may help design a better therapeutic strategy to treat AAN patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vesículas Extracelulares
/
Nefropatias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Biol Toxicol
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China