Identification of kidney injury released circulating osteopontin as causal agent of respiratory failure.
Sci Adv
; 8(8): eabm5900, 2022 02 25.
Article
em En
| MEDLINE
| ID: mdl-35213222
ABSTRACT
Tissue injury can drive secondary organ injury; however, mechanisms and mediators are not well understood. To identify interorgan cross-talk mediators, we used acute kidney injury (AKI)-induced acute lung injury (ALI) as a clinically important example. Using kidney and lung single-cell RNA sequencing after AKI in mice followed by ligand-receptor pairing analysis across organs, kidney ligands to lung receptors, we identify kidney-released circulating osteopontin (OPN) as a novel AKI-ALI mediator. OPN release from kidney tubule cells triggered lung endothelial leakage, inflammation, and respiratory failure. Pharmacological or genetic OPN inhibition prevented AKI-ALI. Transplantation of ischemic wt kidneys caused AKI-ALI, but not of ischemic OPN-global knockout kidneys, identifying kidney-released OPN as necessary interorgan signal to cause AKI-ALI. We show that OPN serum levels are elevated in patients with AKI and correlate with kidney injury. Our results demonstrate feasibility of using ligand-receptor analysis across organs to identify interorgan cross-talk mediators and may have important therapeutic implications in human AKI-ALI and multiorgan failure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Respiratória
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Lesão Pulmonar Aguda
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Injúria Renal Aguda
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
Limite:
Animals
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Female
/
Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article