Hepatic-derived BMP9 is involved in hepatic fibrosis-induced kidney injury through inhibition of renal VEGFA.
Biochem Pharmacol
; 226: 116371, 2024 08.
Article
en En
| MEDLINE
| ID: mdl-38885771
ABSTRACT
Clinical observations suggest that acute kidney injury (AKI) occurs in approximately 20-50% of hospitalized cirrhotic patients, suggesting a link between the liver and kidney. Bone morphogenetic protein 9 (BMP9) is a protein produced primarily by the liver and can act on other tissues at circulating systemic levels. Previous studies have demonstrated that controlling abnormally elevated BMP9 in acute liver injury attenuates liver injury; however, reports on whether BMP9 plays a role in liver injury-induced AKI are lacking. By testing we found that liver injury in mice after bile duct ligation (BDL) was accompanied by a significant upregulation of the kidney injury marker kidney injury molecule (KIM-1). Interestingly, all these impairments were alleviated in the kidneys of hepatic BMP9 knockout (BMP9-KO) mice. Peritubular capillary injury is a key process leading to the progression of AKI, and previous studies have demonstrated that vascular endothelial growth factor A (VEGFA) plays a key role in maintaining the renal microvascular system. In animal experiments, we found that high levels of circulating BMP9 had an inhibitory effect on VEGFA expression, while renal tubular epithelial cell injury was effectively attenuated by VEGFA supplementation in the hypoxia-enriched-oxygen (H/R) constructs of the AKI cell model in both humans and mice. Overall, we found that elevated BMP9 in hepatic fibrosis can affect renal homeostasis by regulating VEGFA expression. Therefore, we believe that targeting BMP9 therapy may be a potential means to address the problem of clinical liver fibrosis combined with AKI.
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Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ratones Noqueados
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Factor A de Crecimiento Endotelial Vascular
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Factor 2 de Diferenciación de Crecimiento
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Lesión Renal Aguda
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Cirrosis Hepática
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Ratones Endogámicos C57BL
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Pharmacol
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido